PCDH19protocadherin 19
Autism Reports / Total Reports
10 / 65Rare Variants / Common Variants
269 / 0Aliases
PCDH19, EFMRAssociated Syndromes
-Chromosome Band
Xq22.1Associated Disorders
SCZ, DD/NDD, ADHD, ID, EPS, ASDRelevance to Autism
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (several studies for each disease).
Molecular Function
A calcium-dependent cell-adhesion protein that is primarily expressed in the brain
External Links
SFARI Genomic Platforms
Reports related to PCDH19 (65 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Highly Cited | X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment | Dibbens LM , et al. (2008) | No | ID, epilepsy |
2 | Highly Cited | Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females | Depienne C , et al. (2009) | No | Delayed or absent speech, autistic features |
3 | Recent Recommendation | Protocadherin-19 is essential for early steps in brain morphogenesis | Emond MR , et al. (2009) | No | - |
4 | Recent Recommendation | Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families | Hynes K , et al. (2009) | No | - |
5 | Primary | Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia | Piton A , et al. (2010) | Yes | SCZ |
6 | Recent Recommendation | Protocadherin 19 mutations in girls with infantile-onset epilepsy | Marini C , et al. (2010) | No | - |
7 | Recent Recommendation | Novel de novo PCDH19 mutations in three unrelated females with epilepsy female restricted mental retardation syndrome | Jamal SM , et al. (2010) | No | ID, epilepsy |
8 | Recent Recommendation | A novel PCDH19 mutation inherited from an unaffected mother | Dimova PS , et al. (2012) | No | MR |
9 | Support | Interpretation of clinical relevance of X-chromosome copy number variations identified in a large cohort of individuals with cognitive disorders and/or congenital anomalies | Willemsen MH , et al. (2012) | No | ASD, ADHD |
10 | Support | Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome | Kwong AK , et al. (2012) | No | ASD, ID |
11 | Recent Recommendation | Focal seizures with affective symptoms are a major feature of PCDH19 gene-related epilepsy | Marini C , et al. (2012) | No | ID, ASD |
12 | Support | Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders | van Harssel JJ , et al. (2013) | No | ID, ASD |
13 | Support | Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 | Carvill GL , et al. (2013) | No | ID, ASD, DD |
14 | Support | PCDH19-related female-limited epilepsy: further details regarding early clinical features and therapeutic efficacy | Higurashi N , et al. (2013) | No | ID, ASD |
15 | Recent Recommendation | Cognitive development in females with PCDH19 gene-related epilepsy | Cappelletti S , et al. (2014) | No | Autistic features |
16 | Support | Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities | Zhang Y , et al. (2015) | No | - |
17 | Support | PCDH19-related epilepsy in two mosaic male patients | Terracciano A , et al. (2016) | No | - |
18 | Support | PCDH19-related epileptic encephalopathy in a male mosaic for a truncating variant | Thiffault I , et al. (2016) | No | ADHD, OCD, ODD |
19 | Support | The clinical spectrum of female epilepsy patients with PCDH19 mutations in a Chinese population | Liu A , et al. (2016) | No | ID, autistic features |
20 | Support | Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes | Parrini E , et al. (2016) | No | - |
21 | Recent Recommendation | Protocadherin 19 (PCDH19) interacts with paraspeckle protein NONO to co-regulate gene expression with estrogen receptor alpha (ER?) | Pham DH , et al. (2017) | No | - |
22 | Support | Male patients affected by mosaic PCDH19 mutations: five new cases | de Lange IM , et al. (2017) | No | ID, ASD |
23 | Recent Recommendation | The female epilepsy protein PCDH19 is a new GABAAR-binding partner that regulates GABAergic transmission as well as migration and morphological maturation of hippocampal neurons | Bassani S , et al. (2018) | No | - |
24 | Recent Recommendation | PCDH19-related epilepsy is associated with a broad neurodevelopmental spectrum | Smith L , et al. (2018) | No | ASD or autistic features |
25 | Support | PCDH19 regulation of neural progenitor cell differentiation suggests asynchrony of neurogenesis as a mechanism contributing to PCDH19 Girls Clustering Epilepsy | Homan CC , et al. (2018) | No | - |
26 | Support | Chinese cases of early infantile epileptic encephalopathy: a novel mutation in the PCDH19 gene was proved in a mosaic male- case report | Tan Y , et al. (2018) | No | - |
27 | Recent Recommendation | A systematic review and meta-analysis of 271 PCDH19-variant individuals identifies psychiatric comorbidities, and association of seizure onset and disease severity | Kolc KL , et al. (2018) | No | - |
28 | Support | PCDH19-related epilepsy in a male with Klinefelter syndrome: Additional evidence supporting PCDH19 cellular interference disease mechanism | Romasko EJ , et al. (2018) | No | - |
29 | Support | Mosaicism and incomplete penetrance of PCDH19 mutations | Liu A , et al. (2018) | No | ASD |
30 | Recent Recommendation | Defining the electroclinical phenotype and outcome of PCDH19-related epilepsy: A multicenter study | Trivisano M , et al. (2018) | No | ASD |
31 | Support | Schizophrenia is a later-onset feature of PCDH19 Girls Clustering Epilepsy | Vlaskamp DRM , et al. (2019) | No | SCZ |
32 | Support | The combination of whole-exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders | Jiao Q , et al. (2019) | No | DD |
33 | Support | Multiplane Calcium Imaging Reveals Disrupted Development of Network Topology in Zebrafish pcdh19 Mutants | Light SEW and Jontes JD (2019) | No | - |
34 | Support | The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children | Long S , et al. (2019) | Yes | - |
35 | Support | A novel PCDH19 missense mutation, c.812G>A (p.Gly271Asp), identified using whole-exome sequencing in a Chinese family with epilepsy female restricted mental retardation syndrome | Zhao X et al. (2020) | No | Autistic features |
36 | Support | A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders | Suzuki T et al. (2020) | Yes | - |
37 | Support | Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression | Yin J et al. (2020) | Yes | Developmental regression, epilepsy/seizures |
38 | Support | The Epilepsy-Related Protein PCDH19 Regulates Tonic Inhibition, GABA A R Kinetics, and the Intrinsic Excitability of Hippocampal Neurons | Serratto GM et al. (2020) | No | - |
39 | Support | - | Pham DH et al. (2021) | No | ASD |
40 | Support | - | Zou D et al. (2021) | No | - |
41 | Support | - | Borghi R et al. (2021) | No | - |
42 | Support | - | Hudson JD et al. (2021) | No | - |
43 | Support | - | Mahjani B et al. (2021) | Yes | - |
44 | Support | - | Hieu NLT et al. (2022) | No | - |
45 | Support | - | Robens BK et al. (2022) | No | - |
46 | Support | - | Cwetsch AW et al. (2022) | Yes | - |
47 | Support | - | Chuan Z et al. (2022) | No | - |
48 | Support | - | Gerosa L et al. (2022) | No | - |
49 | Support | - | Lamers D et al. (2022) | No | - |
50 | Support | - | Nagarajan L et al. (2022) | Yes | - |
51 | Support | - | Johannessen M et al. (2022) | Yes | - |
52 | Support | - | Dell' et al. (2022) | No | - |
53 | Support | - | Zhou X et al. (2022) | Yes | - |
54 | Support | - | Pancho A et al. (2022) | No | - |
55 | Support | - | Zhou W et al. (2023) | No | ASD, SCZ, DD, ID |
56 | Support | - | Chouery E et al. (2023) | Yes | - |
57 | Support | - | Matteo Lenge et al. (2024) | No | - |
58 | Support | - | Luigi Vetri et al. (2024) | No | - |
59 | Support | - | Rebekah de Nys et al. () | No | - |
60 | Support | - | Nami Motosugi et al. (2024) | No | - |
61 | Support | - | Wei Niu et al. (2024) | No | - |
62 | Support | - | Jugeon Park et al. (2024) | No | - |
63 | Support | - | Renata Szalai et al. (2024) | No | ASD, ADHD, DD |
64 | Support | - | Axel Schmidt et al. (2024) | No | DD |
65 | Support | - | Weixing Feng et al. () | No | ASD, DD |
Rare Variants (269)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_loss | De novo | - | - | 30287595 | Liu A , et al. (2018) | |
- | - | copy_number_loss | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
- | - | copy_number_loss | Unknown | - | - | 29377098 | Smith L , et al. (2018) | |
- | - | stop_gained | De novo | - | - | 25499160 | Cappelletti S , et al. (2014) | |
- | - | copy_number_loss | De novo | - | - | 19214208 | Depienne C , et al. (2009) | |
- | - | copy_number_gain | Unknown | - | - | 22796527 | Willemsen MH , et al. (2012) | |
- | - | copy_number_loss | De novo | - | Simplex | 39146709 | Weixing Feng et al. () | |
- | p.Ile508His | frameshift_variant | - | - | - | 20713952 | Marini C , et al. (2010) | |
A>G | - | splice_site_variant | De novo | - | - | 20713952 | Marini C , et al. (2010) | |
c.6G>A | p.Glu2= | synonymous_variant | - | - | - | 19752159 | Hynes K , et al. (2009) | |
delTTTT | - | frameshift_variant | De novo | - | - | 20830798 | Jamal SM , et al. (2010) | |
G>A | p.? | splice_site_variant | De novo | - | - | 20713952 | Marini C , et al. (2010) | |
- | - | copy_number_loss | De novo | - | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.1183C>T | p.Arg395Ter | stop_gained | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
c.402C>A | p.Ile134= | synonymous_variant | - | - | - | 19752159 | Hynes K , et al. (2009) | |
c.655C>T | p.Leu219= | synonymous_variant | - | - | - | 19752159 | Hynes K , et al. (2009) | |
c.1375C>T | p.Gln459Ter | stop_gained | De novo | - | - | 27527380 | Liu A , et al. (2016) | |
c.1825G>T | p.Glu609Ter | stop_gained | Unknown | - | - | 27527380 | Liu A , et al. (2016) | |
c.1133C>G | p.Ser378Ter | stop_gained | De novo | - | - | 30287595 | Liu A , et al. (2018) | |
c.1804C>T | p.Arg602Ter | stop_gained | De novo | - | - | 30287595 | Liu A , et al. (2018) | |
c.139C>T | p.Arg47Ter | stop_gained | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.2873G>A | p.Arg958Gln | missense_variant | - | - | - | 19752159 | Hynes K , et al. (2009) | |
c.1137C>T | p.Gly379= | synonymous_variant | - | - | - | 19752159 | Hynes K , et al. (2009) | |
c.1627C>T | p.Leu543= | synonymous_variant | - | - | - | 19752159 | Hynes K , et al. (2009) | |
c.1683G>A | p.Pro561= | synonymous_variant | - | - | - | 19752159 | Hynes K , et al. (2009) | |
c.83C>A | p.Ser28Ter | stop_gained | De novo | - | - | 20713952 | Marini C , et al. (2010) | |
c.83C>A | p.Ser28Ter | stop_gained | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.619C>T | p.Arg207Ter | stop_gained | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.825C>A | p.Tyr275Ter | stop_gained | Unknown | - | - | 29377098 | Smith L , et al. (2018) | |
- | p.Asp968Glu | frameshift_variant | De novo | - | - | 20713952 | Marini C , et al. (2010) | |
c.2113C>T | p.Arg705Ter | stop_gained | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.729C>A | p.Tyr243Ter | stop_gained | De novo | - | - | 20830798 | Jamal SM , et al. (2010) | |
c.2617-1G>A | - | splice_site_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.812G>A | p.Gly271Asp | missense_variant | Unknown | - | - | 34145886 | Zou D et al. (2021) | |
c.262G>T | p.Asp88Tyr | missense_variant | De novo | - | - | 30287595 | Liu A , et al. (2018) | |
c.1183C>T | p.Arg395Ter | stop_gained | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.1804C>T | p.Arg602Ter | stop_gained | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.471C>A | p.Asp157Glu | missense_variant | De novo | - | - | 27527380 | Liu A , et al. (2016) | |
c.488T>G | p.Val163Gly | missense_variant | De novo | - | - | 27527380 | Liu A , et al. (2016) | |
c.695A>G | p.Asn232Ser | missense_variant | De novo | - | - | 27527380 | Liu A , et al. (2016) | |
c.964G>C | p.Gly322Arg | missense_variant | De novo | - | - | 27527380 | Liu A , et al. (2016) | |
c.317T>A | p.Met106Lys | missense_variant | De novo | - | - | 30287595 | Liu A , et al. (2018) | |
c.471C>G | p.Asp157Glu | missense_variant | De novo | - | - | 30287595 | Liu A , et al. (2018) | |
c.549C>G | p.Asp183Glu | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.1019A>G | p.Asn340Ser | missense_variant | De novo | - | - | 27527380 | Liu A , et al. (2016) | |
c.1184G>C | p.Arg395Pro | missense_variant | De novo | - | - | 27527380 | Liu A , et al. (2016) | |
c.1681C>T | p.Pro561Ser | missense_variant | De novo | - | - | 30287595 | Liu A , et al. (2018) | |
c.798C>G | p.Asp266Glu | missense_variant | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
c.369C>A | p.Asn123Lys | missense_variant | De novo | - | - | 35571021 | Chuan Z et al. (2022) | |
c.695A>G | p.Asn232Ser | missense_variant | Unknown | - | - | 35571021 | Chuan Z et al. (2022) | |
c.462C>G | p.Tyr154Ter | stop_gained | De novo | - | - | 28669061 | de Lange IM , et al. (2017) | |
c.799G>T | p.Glu267Ter | stop_gained | De novo | - | - | 28669061 | de Lange IM , et al. (2017) | |
c.840C>G | p.Tyr280Ter | stop_gained | De novo | - | - | 28669061 | de Lange IM , et al. (2017) | |
c.2675+1G>T | - | splice_site_variant | Unknown | - | - | 39039281 | Axel Schmidt et al. (2024) | |
c.826T>C | p.Ser276Pro | missense_variant | De novo | - | - | 19752159 | Hynes K , et al. (2009) | |
c.344T>A | p.Ile115Lys | missense_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.361G>C | p.Asp121His | missense_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.370G>T | p.Asp124Tyr | missense_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.593G>T | p.Arg198Leu | missense_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.695A>G | p.Asn232Ser | missense_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.1019A>G | p.Asn340Ser | missense_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.1114C>T | p.Arg372Trp | missense_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.1372T>C | p.Tyr458His | missense_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.1435G>A | p.Asp479Asn | missense_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.1441G>A | p.Asp481Asn | missense_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.1013A>G | p.Asp338Gly | missense_variant | De novo | - | - | 39146709 | Weixing Feng et al. () | |
c.1019A>G | p.Asn340Ser | missense_variant | De novo | - | - | 39146709 | Weixing Feng et al. () | |
c.608A>C | p.His203Pro | missense_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.617T>G | p.Phe206Cys | missense_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.695A>G | p.Asn232Ser | missense_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.706C>T | p.Pro236Ser | missense_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.790G>C | p.Asp264His | missense_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.419A>G | p.Glu140Gly | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
- | p.Glu900ArgfsTer8 | frameshift_variant | De novo | - | - | 20713952 | Marini C , et al. (2010) | |
c.326C>G | p.Ser109Ter | stop_gained | De novo | - | Simplex | 35365919 | Hieu NLT et al. (2022) | |
c.1019A>G | p.Asn340Ser | missense_variant | De novo | - | - | 20713952 | Marini C , et al. (2010) | |
c.1129G>C | p.Asp377His | missense_variant | De novo | - | - | 20713952 | Marini C , et al. (2010) | |
c.1211C>T | p.Thr404Ile | missense_variant | De novo | - | - | 20713952 | Marini C , et al. (2010) | |
c.1019A>G | p.Asn340Ser | missense_variant | Unknown | - | - | 22848613 | Kwong AK , et al. (2012) | |
c.1129G>A | p.Asp377Asn | missense_variant | De novo | - | - | 22848613 | Kwong AK , et al. (2012) | |
c.1019A>G | p.Asn340Ser | missense_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.1129G>C | p.Asp377His | missense_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.1211C>T | p.Thr404Ile | missense_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.1298T>C | p.Leu433Pro | missense_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.1537G>C | p.Gly513Arg | missense_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.1700C>T | p.Pro567Leu | missense_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.416C>A | p.Ser139Ter | stop_gained | De novo | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.718G>T | p.Glu240Ter | stop_gained | De novo | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.121A>G | p.Asn41Asp | missense_variant | Unknown | - | Unknown | 32722525 | Yin J et al. (2020) | |
c.2113C>T | p.Arg705Ter | stop_gained | Familial | Paternal | - | 30287595 | Liu A , et al. (2018) | |
c.2656C>T | p.Arg886Ter | stop_gained | De novo | - | Simplex | 39146709 | Weixing Feng et al. () | |
c.1339A>C | p.Asn447His | missense_variant | Unknown | - | - | 27864847 | Parrini E , et al. (2016) | |
c.2656C>T | p.Arg886Ter | stop_gained | De novo | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.64del | p.Leu22SerfsTer8 | frameshift_variant | De novo | - | - | 30287595 | Liu A , et al. (2018) | |
C>G | p.His146Gln | missense_variant | Familial | Maternal | - | 20479760 | Piton A , et al. (2010) | |
c.991A>T | p.Lys331Ter | stop_gained | Unknown | - | Multiplex | 29377098 | Smith L , et al. (2018) | |
c.1681C>T | p.Pro561Ser | missense_variant | Unknown | - | - | 23708187 | Carvill GL , et al. (2013) | |
c.1019A>G | p.Asn340Ser | missense_variant | De novo | - | - | 38256219 | Luigi Vetri et al. (2024) | |
c.1345_1347dup | p.Asn449dup | inframe_insertion | De novo | - | - | 27527380 | Liu A , et al. (2016) | |
c.263A>C | p.Asp88Ala | missense_variant | De novo | - | Simplex | 35571021 | Chuan Z et al. (2022) | |
c.2656C>T | p.Arg886Ter | stop_gained | Familial | Maternal | - | 29377098 | Smith L , et al. (2018) | |
c.2656C>T | p.Arg886Ter | stop_gained | Familial | Paternal | - | 39146709 | Weixing Feng et al. () | |
c.2528T>C | p.Ile843Thr | splice_site_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.859G>T | p.Glu287Ter | stop_gained | De novo | - | Simplex | 19214208 | Depienne C , et al. (2009) | |
c.1682C>G | p.Pro561Arg | missense_variant | Unknown | - | - | 28669061 | de Lange IM , et al. (2017) | |
c.1864G>C | p.Gly622Arg | missense_variant | De novo | - | - | 28669061 | de Lange IM , et al. (2017) | |
c.91G>A | p.Glu31Lys | missense_variant | De novo | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.158dup | p.Asp54GlyfsTer35 | frameshift_variant | De novo | - | - | 30287595 | Liu A , et al. (2018) | |
c.183dup | p.Arg62SerfsTer27 | frameshift_variant | De novo | - | - | 30287595 | Liu A , et al. (2018) | |
c.1681C>T | p.Pro561Ser | missense_variant | De novo | - | Simplex | 29866057 | Tan Y , et al. (2018) | |
c.1966G>C | p.Ala656Pro | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.1192G>T | p.Glu398Ter | stop_gained | Familial | Paternal | - | 20713952 | Marini C , et al. (2010) | |
c.2341del | p.Ser781LeufsTer6 | frameshift_variant | De novo | - | - | 30287595 | Liu A , et al. (2018) | |
c.496T>A | p.Tyr166Asn | missense_variant | De novo | - | Simplex | 35365919 | Hieu NLT et al. (2022) | |
c.369C>A | p.Asn123Lys | missense_variant | De novo | - | Simplex | 39146709 | Weixing Feng et al. () | |
c.665T>A | p.Val222Asp | missense_variant | De novo | - | Simplex | 39146709 | Weixing Feng et al. () | |
c.695A>G | p.Asn232Ser | missense_variant | De novo | - | Simplex | 39146709 | Weixing Feng et al. () | |
c.797A>T | p.Asp266Val | missense_variant | De novo | - | Simplex | 39146709 | Weixing Feng et al. () | |
c.1466_1468del | p.Ser489del | inframe_deletion | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.78del | p.Lys26AsnfsTer4 | frameshift_variant | De novo | - | - | 20830798 | Jamal SM , et al. (2010) | |
c.352G>T | p.Glu118Ter | stop_gained | De novo | - | Multiplex | 19214208 | Depienne C , et al. (2009) | |
c.2656C>T | p.Arg886Ter | stop_gained | De novo | - | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.1178C>T | p.Pro393Leu | missense_variant | De novo | - | - | 25499160 | Cappelletti S , et al. (2014) | |
c.1019A>G | p.Asn340Ser | missense_variant | Familial | Maternal | - | 30287595 | Liu A , et al. (2018) | |
c.1178C>T | p.Pro393Leu | missense_variant | Familial | Paternal | - | 30287595 | Liu A , et al. (2018) | |
c.1191G>C | p.Gln397His | missense_variant | Familial | Paternal | - | 30287595 | Liu A , et al. (2018) | |
c.1240G>A | p.Glu414Lys | missense_variant | Familial | Maternal | - | 30287595 | Liu A , et al. (2018) | |
c.1091dup | p.Tyr366LeufsTer10 | frameshift_variant | De novo | - | - | 27527380 | Liu A , et al. (2016) | |
c.2133del | p.Thr712ProfsTer41 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.2808C>T | p.Asn936%3D | synonymous_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
c.1019A>G | p.Asn340Ser | missense_variant | De novo | - | Simplex | 39146709 | Weixing Feng et al. () | |
c.1183C>T | p.Arg395Ter | missense_variant | De novo | - | Simplex | 39146709 | Weixing Feng et al. () | |
c.1031C>T | p.Pro344Leu | missense_variant | De novo | - | Unknown | 39146709 | Weixing Feng et al. () | |
c.918C>G | p.Tyr306Ter | stop_gained | De novo | - | Simplex | 26765483 | Terracciano A , et al. (2016) | |
c.1019A>G | p.Asn340Ser | missense_variant | Unknown | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.1022A>G | p.Asp341Gly | missense_variant | De novo | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.1031C>T | p.Pro344Leu | missense_variant | De novo | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.1123G>T | p.Asp375Tyr | missense_variant | De novo | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.1780G>C | p.Asp594His | missense_variant | De novo | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.1802G>A | p.Gly601Asp | missense_variant | Unknown | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.2222C>T | p.Ser741Leu | missense_variant | Familial | Paternal | - | 31139143 | Long S , et al. (2019) | |
c.1663del | p.Asp555ThrfsTer14 | frameshift_variant | De novo | - | - | 30945278 | Jiao Q , et al. (2019) | |
c.463G>A | p.Asp155Asn | missense_variant | Familial | Paternal | - | 29377098 | Smith L , et al. (2018) | |
c.463G>C | p.Asp155His | missense_variant | Familial | Paternal | - | 29377098 | Smith L , et al. (2018) | |
c.625A>C | p.Thr209Pro | missense_variant | Familial | Paternal | - | 29377098 | Smith L , et al. (2018) | |
c.434dup | p.Thr146HisfsTer80 | frameshift_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.805del | p.Thr269ProfsTer36 | frameshift_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.2146dup | p.Arg716LysfsTer4 | frameshift_variant | Unknown | - | - | 29377098 | Smith L , et al. (2018) | |
c.152dup | p.Ala52ArgfsTer37 | frameshift_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.2360G>T | p.Arg787Leu | missense_variant | Unknown | - | Simplex | 36980870 | Chouery E et al. (2023) | |
c.242T>G | p.Leu81Arg | missense_variant | De novo | - | Multiplex | 22946748 | Marini C , et al. (2012) | |
c.1020T>G | p.Asn340Lys | missense_variant | Familial | Paternal | - | 29377098 | Smith L , et al. (2018) | |
c.1335C>A | p.Asp445Glu | missense_variant | Familial | Maternal | - | 29377098 | Smith L , et al. (2018) | |
c.1748T>C | p.Ile583Thr | missense_variant | Familial | Paternal | - | 29377098 | Smith L , et al. (2018) | |
c.1091dup | p.Tyr366LeufsTer10 | frameshift_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.1247A>C | p.His416Pro | missense_variant | De novo | - | Multiplex | 39146709 | Weixing Feng et al. () | |
c.958dup | p.Asp320GlyfsTer22 | frameshift_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.2200dup | p.Ile734AsnfsTer3 | frameshift_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.2556dup | p.Glu853ArgfsTer8 | frameshift_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.269A>T | p.Asp90Val | missense_variant | De novo | - | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.1019A>G | p.Asn340Ser | missense_variant | Familial | Maternal | - | 20713952 | Marini C , et al. (2010) | |
c.1240G>C | p.Glu414Gln | missense_variant | Familial | Paternal | - | 20713952 | Marini C , et al. (2010) | |
c.1019A>G | p.Asn340Ser | missense_variant | Familial | Maternal | - | 22946748 | Marini C , et al. (2012) | |
c.1786G>C | p.Asp596His | missense_variant | Familial | Paternal | - | 22946748 | Marini C , et al. (2012) | |
A608CT617 | His203Pro, Phe206Cys | missense_variant | De novo | - | - | 20713952 | Marini C , et al. (2010) | |
c.1521dup | p.Ile508HisfsTer15 | frameshift_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.2762dup | p.Asp921GlufsTer18 | frameshift_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.1019A>G | p.Asn340Ser | missense_variant | De novo | - | Simplex | 19214208 | Depienne C , et al. (2009) | |
c.593G>T | p.Arg198Leu | missense_variant | Unknown | - | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.2490_2493del | p.Thr831SerfsTer2 | frameshift_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.339C>A | p.Cys113Ter | stop_gained | Familial | - | Multi-generational | 27527380 | Liu A , et al. (2016) | |
c.1091dupC | p.Tyr366LeufsTer10 | frameshift_variant | De novo | - | - | 22946748 | Marini C , et al. (2012) | |
c.2463dup | p.Pro822AlafsTer8 | frameshift_variant | De novo | - | - | 35856042 | Nagarajan L et al. (2022) | |
c.1019A>G | p.Asn340Ser | missense_variant | De novo | - | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.2012C>G | p.Ser671Ter | stop_gained | Familial | - | Multi-generational | 27527380 | Liu A , et al. (2016) | |
c.898_899del | p.Val300HisfsTer19 | frameshift_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.2624del | p.Asn875ThrfsTer9 | frameshift_variant | Unknown | - | - | 39039281 | Axel Schmidt et al. (2024) | |
c.497dup | p.Tyr166Ter | frameshift_variant | Unknown | - | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.1352C>T | p.Pro451Leu | missense_variant | De novo | - | Simplex | 26765483 | Terracciano A , et al. (2016) | |
c.1240G>A | p.Glu414Lys | missense_variant | Familial | Maternal | Simplex | 27527380 | Liu A , et al. (2016) | |
c.1508dup | p.Thr504HisfsTer19 | frameshift_variant | De novo | - | Simplex | 29866057 | Tan Y , et al. (2018) | |
c.1687delA | p.Ile553fsTer16 | frameshift_variant | De novo | - | Simplex | 39146709 | Weixing Feng et al. () | |
c.706C>T | p.Pro236Ser | missense_variant | Unknown | Not maternal | - | 29933145 | Romasko EJ , et al. (2018) | |
c.142G>T | p.Glu48Ter | stop_gained | Familial | Paternal | Multiplex | 19214208 | Depienne C , et al. (2009) | |
c.2359C>T | p.Arg787Cys | missense_variant | Unknown | - | Simplex | 23334464 | van Harssel JJ , et al. (2013) | |
c.370G>A | p.Asp124Asn | missense_variant | Familial | Paternal | Multiplex | 27527380 | Liu A , et al. (2016) | |
c.790G>C | p.Asp264His | missense_variant | Familial | Paternal | Multiplex | 27527380 | Liu A , et al. (2016) | |
c.1095_1101del | p.Tyr366SerfsTer201 | frameshift_variant | De novo | - | - | 29377098 | Smith L , et al. (2018) | |
c.370G>A | p.Asp124Asn | missense_variant | Familial | Paternal | Simplex | 26544041 | Zhang Y , et al. (2015) | |
c.463G>C | p.Asp155His | missense_variant | Familial | Paternal | Simplex | 39146709 | Weixing Feng et al. () | |
c.695A>G | p.Asn232Ser | missense_variant | Familial | Paternal | Simplex | 39146709 | Weixing Feng et al. () | |
c.2341dup | p.Ile781AsnfsTer3 | frameshift_variant | De novo | - | Simplex | 39146709 | Weixing Feng et al. () | |
c.2156T>G | p.Leu719Ter | stop_gained | Familial | Paternal | Simplex | 23712037 | Higurashi N , et al. (2013) | |
c.1048C>G | p.Ser349Ter | stop_gained | Familial | Paternal | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.830_831delinsAA | p.Phe277Ter | stop_gained | De novo | - | Simplex | 38891919 | Renata Szalai et al. (2024) | |
c.1091dup | p.Tyr366LeufsTer10 | frameshift_variant | De novo | - | - | 25499160 | Cappelletti S , et al. (2014) | |
c.823T>A | p.Tyr275Asn | missense_variant | Familial | Maternal | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.1091del | p.Pro364ArgfsTer4 | frameshift_variant | De novo | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.812G>A | p.Gly271Asp | missense_variant | Familial | - | Extended multiplex | 32314541 | Zhao X et al. (2020) | |
c.695A>G | p.Asn232Ser | missense_variant | Familial | - | Multi-generational | 36970538 | Zhou W et al. (2023) | |
c.2977G>A | p.Asp993Asn | missense_variant | Familial | Maternal | Unknown | 32530565 | Suzuki T et al. (2020) | |
c.1019A>G | p.Asn340Ser | missense_variant | Familial | Maternal | Simplex | 39146709 | Weixing Feng et al. () | |
c.1729A>C | p.Ile577Leu | missense_variant | Familial | Maternal | Simplex | 39146709 | Weixing Feng et al. () | |
c.1802G>A | p.Gly601Asp | missense_variant | Familial | Maternal | Simplex | 39146709 | Weixing Feng et al. () | |
c.1863dup | p.Gly622TrpfsTer18 | frameshift_variant | De novo | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.2851del | p.Thr951LeufsTer36 | splice_site_variant | Familial | Maternal | - | 30287595 | Liu A , et al. (2018) | |
c.2760T>A | p.Asp920Glu | missense_variant | Familial | - | Multi-generational | 36970538 | Zhou W et al. (2023) | |
c.2999C>T | p.Ala1000Val | missense_variant | Familial | Paternal | Simplex | 39146709 | Weixing Feng et al. () | |
c.1006G>A | p.Val336Met | missense_variant | Familial | Paternal | Simplex | 35978409 | Dell' et al. (2022) | |
c.1014C>A | p.Asp338Glu | missense_variant | Familial | Paternal | Simplex | 35978409 | Dell' et al. (2022) | |
c.605C>A | p.Ser202Ter | stop_gained | Unknown | Not maternal | Simplex | 27016041 | Thiffault I , et al. (2016) | |
c.1091dupC | p.Tyr366LeufsTer10 | frameshift_variant | De novo | - | - | 23334464 | van Harssel JJ , et al. (2013) | |
c.134_135del | p.Asp45GlyfsTer43 | frameshift_variant | Familial | Paternal | - | 30287595 | Liu A , et al. (2018) | |
c.497dup | p.Tyr166Ter | frameshift_variant | Familial | - | Multi-generational | 30287595 | Liu A , et al. (2018) | |
c.1091dup | p.Tyr366LeufsTer10 | frameshift_variant | Familial | Paternal | - | 29377098 | Smith L , et al. (2018) | |
c.3070G>A | p.Asp1024Asn | missense_variant | Familial | Maternal | Simplex | 36980870 | Chouery E et al. (2023) | |
c.506del | p.Thr169SerfsTer43 | frameshift_variant | De novo | - | Simplex | 19214208 | Depienne C , et al. (2009) | |
c.357del | p.Lys120ArgfsTer3 | frameshift_variant | Unknown | - | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.918C>G | p.Tyr306Ter | stop_gained | Familial | Paternal | Multi-generational | 29866057 | Tan Y , et al. (2018) | |
c.2564dup | p.Asn855LysfsTer6 | frameshift_variant | Familial | Maternal | - | 22633638 | Dimova PS , et al. (2012) | |
c.1628T>C | p.Leu543Pro | missense_variant | Familial | Paternal | Simplex | 19214208 | Depienne C , et al. (2009) | |
c.2873G>A | p.Arg958Gln | missense_variant | Familial | Paternal | Simplex | 23708187 | Carvill GL , et al. (2013) | |
c.416C>T | p.Ser139Leu | missense_variant | Familial | Maternal | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.469G>A | p.Asp157Asn | missense_variant | Familial | Maternal | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.3319C>G | p.Arg1107Gly | missense_variant | Familial | Paternal | Simplex | 19214208 | Depienne C , et al. (2009) | |
c.361G>A | p.Asp121Asn | missense_variant | Familial | Maternal | Multiplex | 19214208 | Depienne C , et al. (2009) | |
c.1019A>G | p.Asn340Ser | missense_variant | Familial | Maternal | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.1787A>T | p.Asp596Val | missense_variant | Familial | Paternal | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.1091dup | p.Tyr366LeufsTer10 | frameshift_variant | Unknown | - | Unknown | 23712037 | Higurashi N , et al. (2013) | |
c.498C>G | p.Tyr166Ter | stop_gained | Familial | Maternal | Multi-generational | 29377098 | Smith L , et al. (2018) | |
c.595G>C | p.Glu199Gln | missense_variant | Unknown | Not maternal | Simplex | 19214208 | Depienne C , et al. (2009) | |
c.1671C>G | p.Asn557Lys | missense_variant | Familial | Paternal | Multiplex | 18469813 | Dibbens LM , et al. (2008) | |
c.1682C>T | p.Pro561Leu | missense_variant | Familial | Maternal | Simplex | 38891919 | Renata Szalai et al. (2024) | |
c.2123_2124del | p.Lys708ArgfsTer11 | frameshift_variant | Familial | Maternal | - | 30945278 | Jiao Q , et al. (2019) | |
c.1976_1977insGTCCT | p.Leu659fsTer2 | frameshift_variant | De novo | - | Simplex | 39146709 | Weixing Feng et al. () | |
c.166del | p.Arg56GlyfsTer16 | frameshift_variant | Familial | Maternal | Simplex | 39146709 | Weixing Feng et al. () | |
c.253C>T | p.Gln85Ter | stop_gained | Familial | Paternal | Multi-generational | 18469813 | Dibbens LM , et al. (2008) | |
c.1711G>T | p.Gly571Cys | missense_variant | Familial | Maternal | Multiplex | 38891919 | Renata Szalai et al. (2024) | |
c.1091del | p.Pro364ArgfsTer4 | frameshift_variant | Familial | Paternal | Multiplex | 27527380 | Liu A , et al. (2016) | |
c.2685del | p.Phe896SerfsTer4 | frameshift_variant | Familial | Paternal | Simplex | 39146709 | Weixing Feng et al. () | |
c.1300_1301del | p.Gln434GlufsTer11 | frameshift_variant | De novo | - | Multiplex | 22946748 | Marini C , et al. (2012) | |
c.859G>T | p.Glu287Ter | stop_gained | Familial | Paternal | Multi-generational | 19214208 | Depienne C , et al. (2009) | |
c.1987del | p.Ser663ProfsTer13 | frameshift_variant | Familial | Paternal | Multiplex | 30287595 | Liu A , et al. (2018) | |
c.1019A>G | p.Asn340Ser | missense_variant | Familial | Maternal | Multi-generational | 27527380 | Liu A , et al. (2016) | |
c.1091dup | p.Tyr366LeufsTer10 | frameshift_variant | Familial | Paternal | Simplex | 39146709 | Weixing Feng et al. () | |
c.2012C>G | p.Ser671Ter | stop_gained | Familial | Paternal | Multi-generational | 18469813 | Dibbens LM , et al. (2008) | |
c.1152_1180del | p.Gln385SerfsTer6 | frameshift_variant | De novo | - | Simplex | 38891919 | Renata Szalai et al. (2024) | |
c.339dup | p.Val114ArgfsTer112 | frameshift_variant | Familial | - | Multi-generational | 30287595 | Liu A , et al. (2018) | |
c.1091del | p.Pro364ArgfsTer4 | frameshift_variant | Familial | Paternal | Multiplex | 26544041 | Zhang Y , et al. (2015) | |
c.416C>T | p.Ser139Leu | missense_variant | Familial | Paternal | Extended multiplex | 39146709 | Weixing Feng et al. () | |
c.1004G>A | p.Ser335Asn | missense_variant | Familial | Paternal | Multi-generational | 29377098 | Smith L , et al. (2018) | |
c.1342G>A | p.Asp448Asn | missense_variant | Familial | Maternal | Multi-generational | 29377098 | Smith L , et al. (2018) | |
c.1873A>G | p.Arg625Gly | missense_variant | Familial | Maternal | Multi-generational | 29377098 | Smith L , et al. (2018) | |
c.1178C>T | p.Pro393Leu | missense_variant | Familial | Paternal | Extended multiplex | 39146709 | Weixing Feng et al. () | |
c.1191G>C | p.Gln397His | missense_variant | Familial | Paternal | Extended multiplex | 39146709 | Weixing Feng et al. () | |
c.1322T>A | p.Val441Glu | missense_variant | Familial | Paternal | Extended multiplex | 39146709 | Weixing Feng et al. () | |
c.1408_1417del | p.Ala470SerfsTer96 | frameshift_variant | Familial | Paternal | Simplex | 27527380 | Liu A , et al. (2016) | |
c.1322T>A | p.Val441Glu | missense_variant | Familial | Paternal | Multi-generational | 18469813 | Dibbens LM , et al. (2008) | |
c.1264_1276del | p.Thr422AlafsTer143 | frameshift_variant | Familial | Paternal | Simplex | 39146709 | Weixing Feng et al. () | |
c.1068_1071delinsCA | p.Glu357SerfsTer18 | frameshift_variant | De novo | - | Simplex | 35860011 | Johannessen M et al. (2022) | |
c.1031C>T | p.Pro344Leu | missense_variant | Familial | Paternal | Extended multiplex | 38891919 | Renata Szalai et al. (2024) | |
c.134_135del | p.Asp45GlyfsTer43 | frameshift_variant | Familial | Paternal | Multiplex | 23712037 | Higurashi N , et al. (2013) | |
c.824A>C | p.Tyr275Ser | missense_variant | Familial | Maternal | Multi-generational | 23334464 | van Harssel JJ , et al. (2013) | |
c.1017del | p.Asn340MetfsTer28 | frameshift_variant | Familial | Maternal | Multi-generational | 27527380 | Liu A , et al. (2016) | |
c.749del | p.Asn250ThrfsTer55 | frameshift_variant | Familial | Paternal | Extended multiplex | 39146709 | Weixing Feng et al. () | |
c.359del | p.Lys120ArgfsTer3 | frameshift_variant | Familial | Maternal and paternal | Multiplex | 18469813 | Dibbens LM , et al. (2008) | |
c.1036_1037insATCAA | p.Ile346AsnfsTer24 | frameshift_variant | Familial | - | Multi-generational | 19214208 | Depienne C , et al. (2009) | |
c.1094dup | p.Tyr366LeufsTer10 | frameshift_variant | Familial | Maternal and paternal | Multi-generational | 18469813 | Dibbens LM , et al. (2008) | |
c.2030dup | p.Leu677PhefsTer43 | frameshift_variant | Familial | Maternal and paternal | Multi-generational | 18469813 | Dibbens LM , et al. (2008) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence, Syndromic
Score Delta: Score remained at 1S
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
7/1/2020
Score remained at 1
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies). Phenotypic characterization of 38 individuals with pathogenic or potentially pathogenic variants in the PCDH19 gene in Smith et al., 2018 revealed that autistic features were present in 22/38 (58%), of whom 12 had a formal diagnosis of autism spectrum disorder. A systemic review and meta-analysis of 271 individuals with PCDH19 variants in Kolc et al., 2018 determined that of the 213 cases where psychiatric information was available, autistic features were most prominent (19.7%), followed by hyperactivity and/or attention deficit (11.7%), and behavioral disturbances (6.1%). Trivisano et al., 2018 described a cohort of 61 patients with PCDH19-related epilepsy followed in 15 Italian epilepsy centers and reported that autism or autistic features was present in 31 individuals.
Reports Added
[A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders2020] [Next Generation Sequencing of 134 Children with Autism Spectrum Disorder and Regression2020] [The Epilepsy-Related Protein PCDH19 Regulates Tonic Inhibition, GABA A R Kinetics, and the Intrinsic Excitability of Hippocampal Neurons2020]4/1/2020
Score remained at 1
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies). Phenotypic characterization of 38 individuals with pathogenic or potentially pathogenic variants in the PCDH19 gene in Smith et al., 2018 revealed that autistic features were present in 22/38 (58%), of whom 12 had a formal diagnosis of autism spectrum disorder. A systemic review and meta-analysis of 271 individuals with PCDH19 variants in Kolc et al., 2018 determined that of the 213 cases where psychiatric information was available, autistic features were most prominent (19.7%), followed by hyperactivity and/or attention deficit (11.7%), and behavioral disturbances (6.1%). Trivisano et al., 2018 described a cohort of 61 patients with PCDH19-related epilepsy followed in 15 Italian epilepsy centers and reported that autism or autistic features was present in 31 individuals.
10/1/2019
Increased from S to 1
New Scoring Scheme
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies). Phenotypic characterization of 38 individuals with pathogenic or potentially pathogenic variants in the PCDH19 gene in Smith et al., 2018 revealed that autistic features were present in 22/38 (58%), of whom 12 had a formal diagnosis of autism spectrum disorder. A systemic review and meta-analysis of 271 individuals with PCDH19 variants in Kolc et al., 2018 determined that of the 213 cases where psychiatric information was available, autistic features were most prominent (19.7%), followed by hyperactivity and/or attention deficit (11.7%), and behavioral disturbances (6.1%). Trivisano et al., 2018 described a cohort of 61 patients with PCDH19-related epilepsy followed in 15 Italian epilepsy centers and reported that autism or autistic features was present in 31 individuals.
Reports Added
[New Scoring Scheme]7/1/2019
Increased from S to S
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies). Phenotypic characterization of 38 individuals with pathogenic or potentially pathogenic variants in the PCDH19 gene in Smith et al., 2018 revealed that autistic features were present in 22/38 (58%), of whom 12 had a formal diagnosis of autism spectrum disorder. A systemic review and meta-analysis of 271 individuals with PCDH19 variants in Kolc et al., 2018 determined that of the 213 cases where psychiatric information was available, autistic features were most prominent (19.7%), followed by hyperactivity and/or attention deficit (11.7%), and behavioral disturbances (6.1%). Trivisano et al., 2018 described a cohort of 61 patients with PCDH19-related epilepsy followed in 15 Italian epilepsy centers and reported that autism or autistic features was present in 31 individuals.
4/1/2019
Increased from S to S
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies). Phenotypic characterization of 38 individuals with pathogenic or potentially pathogenic variants in the PCDH19 gene in Smith et al., 2018 revealed that autistic features were present in 22/38 (58%), of whom 12 had a formal diagnosis of autism spectrum disorder. A systemic review and meta-analysis of 271 individuals with PCDH19 variants in Kolc et al., 2018 determined that of the 213 cases where psychiatric information was available, autistic features were most prominent (19.7%), followed by hyperactivity and/or attention deficit (11.7%), and behavioral disturbances (6.1%). Trivisano et al., 2018 described a cohort of 61 patients with PCDH19-related epilepsy followed in 15 Italian epilepsy centers and reported that autism or autistic features was present in 31 individuals.
1/1/2019
Increased from S to S
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies). Phenotypic characterization of 38 individuals with pathogenic or potentially pathogenic variants in the PCDH19 gene in Smith et al., 2018 revealed that autistic features were present in 22/38 (58%), of whom 12 had a formal diagnosis of autism spectrum disorder. A systemic review and meta-analysis of 271 individuals with PCDH19 variants in Kolc et al., 2018 determined that of the 213 cases where psychiatric information was available, autistic features were most prominent (19.7%), followed by hyperactivity and/or attention deficit (11.7%), and behavioral disturbances (6.1%). Trivisano et al., 2018 described a cohort of 61 patients with PCDH19-related epilepsy followed in 15 Italian epilepsy centers and reported that autism or autistic features was present in 31 individuals.
10/1/2018
Increased from S to S
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies). Phenotypic characterization of 38 individuals with pathogenic or potentially pathogenic variants in the PCDH19 gene in Smith et al., 2018 revealed that autistic features were present in 22/38 (58%), of whom 12 had a formal diagnosis of autism spectrum disorder. A systemic review and meta-analysis of 271 individuals with PCDH19 variants in Kolc et al., 2018 determined that of the 213 cases where psychiatric information was available, autistic features were most prominent (19.7%), followed by hyperactivity and/or attention deficit (11.7%), and behavioral disturbances (6.1%). Trivisano et al., 2018 described a cohort of 61 patients with PCDH19-related epilepsy followed in 15 Italian epilepsy centers and reported that autism or autistic features was present in 31 individuals.
7/1/2018
Increased from S to S
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies). Phenotypic characterization of 38 individuals with pathogenic or potentially pathogenic variants in the PCDH19 gene in Smith et al., 2018 revealed that autistic features were present in 22/38 (58%), of whom 12 had a formal diagnosis of autism spectrum disorder. A systemic review and meta-analysis of 271 individuals with PCDH19 variants in Kolc et al., 2018 determined that of the 213 cases where psychiatric information was available, autistic features were most prominent (19.7%), followed by hyperactivity and/or attention deficit (11.7%), and behavioral disturbances (6.1%).
Reports Added
[Chinese cases of early infantile epileptic encephalopathy: a novel mutation in the PCDH19 gene was proved in a mosaic male- case report.2018] [A systematic review and meta-analysis of 271 PCDH19-variant individuals identifies psychiatric comorbidities, and association of seizure onset and ...2018] [PCDH19-related epilepsy in a male with Klinefelter syndrome: Additional evidence supporting PCDH19 cellular interference disease mechanism.2018]7/1/2017
Increased from S to S
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies).
Reports Added
[Male patients affected by mosaic PCDH19 mutations: five new cases.2017] [Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females.2009] [PCDH19-related epilepsy in two mosaic male patients.2016] [PCDH19-related epileptic encephalopathy in a male mosaic for a truncating variant.2016]4/1/2017
Increased from S to S
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies).
Reports Added
[Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia.2010] [Interpretation of clinical relevance of X-chromosome copy number variations identified in a large cohort of individuals with cognitive disorders an...2012] [X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment.2008] [Novel de novo PCDH19 mutations in three unrelated females with epilepsy female restricted mental retardation syndrome.2010] [Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families.2009] [Protocadherin 19 mutations in girls with infantile-onset epilepsy.2010] [A novel PCDH19 mutation inherited from an unaffected mother.2012] [Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.2012] [Focal seizures with affective symptoms are a major feature of PCDH19 gene-related epilepsy.2012] [Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders.2013] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [PCDH19-related female-limited epilepsy: further details regarding early clinical features and therapeutic efficacy.2013] [Cognitive development in females with PCDH19 gene-related epilepsy.2014] [Protocadherin-19 is essential for early steps in brain morphogenesis.2009] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015] [The Clinical Spectrum of Female Epilepsy Patients with PCDH19 Mutations in a Chinese Population.2016] [Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric Epilepsies Identifies Causative Mutations in 30 Different Genes.2016] [Protocadherin 19 (PCDH19) interacts with paraspeckle protein NONO to co-regulate gene expression with estrogen receptor alpha (ER).2017]1/1/2017
Increased from S to S
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies).
7/1/2016
Increased from S to S
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies).
1/1/2016
Increased from S to S
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies).
Reports Added
[Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia.2010] [Interpretation of clinical relevance of X-chromosome copy number variations identified in a large cohort of individuals with cognitive disorders an...2012] [X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment.2008] [Novel de novo PCDH19 mutations in three unrelated females with epilepsy female restricted mental retardation syndrome.2010] [Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families.2009] [Protocadherin 19 mutations in girls with infantile-onset epilepsy.2010] [A novel PCDH19 mutation inherited from an unaffected mother.2012] [Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome.2012] [Focal seizures with affective symptoms are a major feature of PCDH19 gene-related epilepsy.2012] [Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders.2013] [Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.2013] [PCDH19-related female-limited epilepsy: further details regarding early clinical features and therapeutic efficacy.2013] [Cognitive development in females with PCDH19 gene-related epilepsy.2014] [Protocadherin-19 is essential for early steps in brain morphogenesis.2009] [Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.2015]1/1/2015
Increased from S to S
Description
Rare mutations in the PCDH19 gene have been identified with autism and schizophrenia (Piton et al., 2011) as well as with epilepsy and mental retardation limited to females (EFMR) and epilepsy alone (Dibbens et al., 2008 and other studies).
Krishnan Probability Score
Score 0.57206658213999
Ranking 726/25841 scored genes
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ExAC Score
Score 0.97715851271551
Ranking 2208/18225 scored genes
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Sanders TADA Score
Score 0.94739465444301
Ranking 17258/18665 scored genes
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Zhang D Score
Score 0.090558776808564
Ranking 6322/20870 scored genes
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