AHDC1AT-hook DNA binding motif containing 1
Autism Reports / Total Reports
3 / 13Rare Variants / Common Variants
54 / 0Aliases
AHDC1, MRD25Associated Syndromes
Xia-Gibbs syndromeGenetic Category
Rare Single Gene Mutation, SyndromicChromosome Band
1p36.11-p35.3Associated Disorders
ASDRelevance to Autism
Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria.
Molecular Function
This gene encodes a protein containing two AT-hooks, which likely function in DNA binding. Mutations in this gene were found in individuals with Xia-Gibbs syndrome (OMIM 615829), a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea (Xia et al., 2014).
Reports related to AHDC1 (13 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | De novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea. | Xia F , et al. (2014) | No | - |
2 | Primary | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
3 | Support | MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus. | Quintero-Rivera F , et al. (2015) | Yes | Congenital heart defects |
4 | Recent Recommendation | De novo truncating variants in the AHDC1 gene encoding the AT-hook DNA-binding motif-containing protein 1 are associated with intellectual disabili... | Yang H , et al. (2016) | No | ASD |
5 | Support | Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability | Lelieveld SH et al. (2016) | No | - |
6 | Support | The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies. | Redin C , et al. (2016) | No | - |
7 | Support | Prevalence and architecture of de novo mutations in developmental disorders | et al. (2017) | No | - |
8 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay. | Bowling KM , et al. (2017) | No | - |
9 | Support | Exome Pool-Seq in neurodevelopmental disorders. | Popp B , et al. (2017) | No | Behavioral anomalies, microcephaly |
10 | Recent Recommendation | The phenotypic spectrum of Xia-Gibbs syndrome. | Jiang Y , et al. (2018) | No | ASD |
11 | Support | Variable Clinical Manifestations of Xia-Gibbs syndrome: Findings of Consecutively Identified Cases at a Single Children's Hospital. | Ritter AL , et al. (2018) | No | ASD |
12 | Support | Xia-Gibbs Syndrome in adulthood: a case report with insight into the natural history of the condition. | Murdock DR , et al. (2019) | No | - |
13 | Support | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | - |
Rare Variants (54)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_loss | Unknown | - | - | 30152016 | Ritter AL , et al. (2018) | |
c.1759C>T | p.Arg587Ter | stop_gained | De novo | NA | - | 28135719 | et al. (2017) | |
c.2188G>T | p.Glu730Ter | stop_gained | De novo | NA | - | 28135719 | et al. (2017) | |
c.2773C>T | p.Arg925Ter | stop_gained | De novo | NA | - | 28135719 | et al. (2017) | |
c.2448C>A | p.Tyr816Ter | stop_gained | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1480A>T | p.Lys494Ter | stop_gained | De novo | NA | - | 27148574 | Yang H , et al. (2016) | |
c.784C>T | p.Gln262Ter | stop_gained | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
- | - | translocation | De novo | NA | Simplex | 25574029 | Quintero-Rivera F , et al. (2015) | |
c.3814C>T | p.Arg1272Ter | stop_gained | De novo | NA | - | 29158550 | Popp B , et al. (2017) | |
c.1706C>T | p.Ala569Val | stop_gained | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
c.2062C>T | p.Arg688Ter | stop_gained | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
c.2644C>T | p.Gln882Ter | stop_gained | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
c.2706C>G | p.Ser902Arg | stop_gained | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
c.2908C>T | p.Gln970Ter | stop_gained | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
c.979C>T | p.Gln327Ter | stop_gained | Unknown | - | - | 30622101 | Murdock DR , et al. (2019) | |
c.2002C>T | p.Arg668Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.2495G>A | p.Arg832His | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.2866C>T | p.Arg956Cys | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.3989C>A | p.Ser1330Ter | stop_gained | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
c.692C>T | p.Pro231Leu | stop_gained | De novo | NA | - | 30152016 | Ritter AL , et al. (2018) | |
c.3331C>T | p.Arg1111Trp | missense_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.2473C>T | p.Gln825Ter | stop_gained | De novo | NA | - | 30152016 | Ritter AL , et al. (2018) | |
c.1231G>A | p.Gly411Ser | missense_variant | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.1819G>A | p.Asp607Asn | missense_variant | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.3805C>T | p.Arg1269Trp | missense_variant | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.2520del | p.Arg841AlafsTer91 | frameshift_variant | De novo | NA | - | 28135719 | et al. (2017) | |
c.2188del | p.Glu730ArgfsTer2 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1788_1789del | p.Gln598AlafsTer44 | frameshift_variant | De novo | NA | - | 28135719 | et al. (2017) | |
c.2248_2249del | p.Leu750ValfsTer17 | frameshift_variant | De novo | NA | - | 28135719 | et al. (2017) | |
c.677_680dup | p.Glu228ProfsTer4 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.1122dup | p.Gly375ArgfsTer3 | frameshift_variant | De novo | NA | - | 27148574 | Yang H , et al. (2016) | |
c.4288dup | p.Gln1430ProfsTer51 | frameshift_variant | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.1945del | p.Ala649ProfsTer83 | frameshift_variant | De novo | NA | - | 27148574 | Yang H , et al. (2016) | |
c.1348del | p.Glu450SerfsTer2 | frameshift_variant | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
c.1881del | p.Gln627HisfsTer105 | frameshift_variant | De novo | NA | - | 27148574 | Yang H , et al. (2016) | |
c.3809del | p.Gln1270ArgfsTer75 | frameshift_variant | De novo | NA | - | 27148574 | Yang H , et al. (2016) | |
c.1162del | p.Asp388IlefsTer64 | frameshift_variant | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
c.1453del | p.Leu485TrpfsTer14 | frameshift_variant | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
c.1624del | p.Ile542PhefsTer43 | frameshift_variant | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
c.1541C>T | p.Ser514Leu | missense_variant | De novo | NA | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.1818dup | p.Asp607ArgfsTer36 | frameshift_variant | De novo | NA | - | 30152016 | Ritter AL , et al. (2018) | |
c.3427dup | p.Leu1143ProfsTer23 | frameshift_variant | De novo | NA | - | 30152016 | Ritter AL , et al. (2018) | |
c.807del | p.Glu270SerfsTer19 | frameshift_variant | De novo | NA | - | 27479843 | Lelieveld SH et al. (2016) | |
c.2373_2374del | p.Cys791TrpfsTer57 | frameshift_variant | De novo | NA | - | 27148574 | Yang H , et al. (2016) | |
c.2529_2545del | p.Asp845ArgfsTer40 | frameshift_variant | De novo | NA | - | 27148574 | Yang H , et al. (2016) | |
c.2229del | p.Ser744ProfsTer188 | frameshift_variant | De novo | NA | - | 28554332 | Bowling KM , et al. (2017) | |
c.1122del | p.Pro376LeufsTer76 | frameshift_variant | De novo | NA | - | 27479843 | Lelieveld SH et al. (2016) | |
c.1402dup | p.Cys468LeufsTer49 | frameshift_variant | De novo | NA | - | 27479843 | Lelieveld SH et al. (2016) | |
c.3019_3020insAGCCT | p.Ser1007LysfsTer137 | frameshift_variant | De novo | NA | - | 28135719 | et al. (2017) | |
c.2547del | p.Ser850ProfsTer82 | frameshift_variant | De novo | NA | Simplex | 24791903 | Xia F , et al. (2014) | |
c.1306_1307del | p.Pro436ThrfsTer80 | frameshift_variant | De novo | NA | - | 29696776 | Jiang Y , et al. (2018) | |
c.2898del | p.Tyr967ThrfsTer175 | frameshift_variant | De novo | NA | Simplex | 24791903 | Xia F , et al. (2014) | |
c.1758dup | p.Arg587ThrfsTer56 | frameshift_variant | De novo | NA | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.2373_2374del | p.Cys791TrpfsTer57 | frameshift_variant | De novo | NA | Simplex | 24791903 | Xia F , et al. (2014) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence


Mutations in the AHDC1 gene were found in four individuals presenting with a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea, which was subsequently classified as Xia-Gibbs syndrome (OMIM 615829), (Xia et al., 2014). One of the original subjects from the Xia et al., 2014 study (subject 4) is described as having "noncommunicating autism" as a clinical feature in Table 1. Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria. An additional 14 previously unreported individuals with de novo truncating mutations in the AHDC1 gene were presented in Jiang et al., 2018; three of these novel cases were reported to have had a prior diagnosis of autism or ASD.
Score Delta: Score remained at 3S
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.
10/1/2020

Score remained at 3S
Description
Mutations in the AHDC1 gene were found in four individuals presenting with a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea, which was subsequently classified as Xia-Gibbs syndrome (OMIM 615829), (Xia et al., 2014). One of the original subjects from the Xia et al., 2014 study (subject 4) is described as having "noncommunicating autism" as a clinical feature in Table 1. Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria. An additional 14 previously unreported individuals with de novo truncating mutations in the AHDC1 gene were presented in Jiang et al., 2018; three of these novel cases were reported to have had a prior diagnosis of autism or ASD.
10/1/2019

Decreased from 3S to 1
New Scoring Scheme
Description
Mutations in the AHDC1 gene were found in four individuals presenting with a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea, which was subsequently classified as Xia-Gibbs syndrome (OMIM 615829), (Xia et al., 2014). One of the original subjects from the Xia et al., 2014 study (subject 4) is described as having "noncommunicating autism" as a clinical feature in Table 1. Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria. An additional 14 previously unreported individuals with de novo truncating mutations in the AHDC1 gene were presented in Jiang et al., 2018; three of these novel cases were reported to have had a prior diagnosis of autism or ASD.
Reports Added
[New Scoring Scheme]1/1/2019

Decreased from 3S to 3S
Description
Mutations in the AHDC1 gene were found in four individuals presenting with a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea, which was subsequently classified as Xia-Gibbs syndrome (OMIM 615829), (Xia et al., 2014). One of the original subjects from the Xia et al., 2014 study (subject 4) is described as having "noncommunicating autism" as a clinical feature in Table 1. Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria. An additional 14 previously unreported individuals with de novo truncating mutations in the AHDC1 gene were presented in Jiang et al., 2018; three of these novel cases were reported to have had a prior diagnosis of autism or ASD.
10/1/2018

Decreased from 3S to 3S
Description
Mutations in the AHDC1 gene were found in four individuals presenting with a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea, which was subsequently classified as Xia-Gibbs syndrome (OMIM 615829), (Xia et al., 2014). One of the original subjects from the Xia et al., 2014 study (subject 4) is described as having "noncommunicating autism" as a clinical feature in Table 1. Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria. An additional 14 previously unreported individuals with de novo truncating mutations in the AHDC1 gene were presented in Jiang et al., 2018; three of these novel cases were reported to have had a prior diagnosis of autism or ASD.
4/1/2018

Decreased from 3S to 3.3 + S
Description
3S
Reports Added
[The phenotypic spectrum of Xia-Gibbs syndrome.2018]10/1/2017

Decreased from 3S to 3S
Description
Mutations in the AHDC1 gene were found in four individuals presenting with a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea, which was subsequently classified as Xia-Gibbs syndrome (OMIM 615829), (Xia et al., 2014). One of the original subjects from the Xia et al., 2014 study (subject 4) is described as having "noncommunicating autism" as a clinical feature in Table 1. Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria.
Reports Added
[Exome Pool-Seq in neurodevelopmental disorders.2017]4/1/2017

Decreased from 3S to 3S
Description
Mutations in the AHDC1 gene were found in four individuals presenting with a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea, which was subsequently classified as Xia-Gibbs syndrome (OMIM 615829), (Xia et al., 2014). One of the original subjects from the Xia et al., 2014 study (subject 4) is described as having "noncommunicating autism" as a clinical feature in Table 1. Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria.
Reports Added
[The contribution of de novo coding mutations to autism spectrum disorder2014] [De novo truncating variants in the AHDC1 gene encoding the AT-hook DNA-binding motif-containing protein 1 are associated with intellectual disabili...2016] [De novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea.2014] [MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus.2015] [Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability2016] [The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies.2016] [Genomic diagnosis for children with intellectual disability and/or developmental delay.2017]10/1/2016

Decreased from 3S to 3S
Description
Mutations in the AHDC1 gene were found in four individuals presenting with a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea, which was subsequently classified as Xia-Gibbs syndrome (OMIM 615829), (Xia et al., 2014). One of the original subjects from the Xia et al., 2014 study (subject 4) is described as having "noncommunicating autism" as a clinical feature in Table 1. Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria.
7/1/2016

Decreased from 3S to 3S
Description
Mutations in the AHDC1 gene were found in four individuals presenting with a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea, which was subsequently classified as Xia-Gibbs syndrome (OMIM 615829), (Xia et al., 2014). One of the original subjects from the Xia et al., 2014 study (subject 4) is described as having "noncommunicating autism" as a clinical feature in Table 1. Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria.
4/1/2016

Increased from to 3S
Description
Mutations in the AHDC1 gene were found in four individuals presenting with a syndrome characterized by intellectual disability, expressive language delay, hypotonia, and obstructive sleep apnea, which was subsequently classified as Xia-Gibbs syndrome (OMIM 615829), (Xia et al., 2014). One of the original subjects from the Xia et al., 2014 study (subject 4) is described as having "noncommunicating autism" as a clinical feature in Table 1. Novel de novo variants in the AHDC1 gene (one frameshift, one missense variant predicted to be benign) were identified in ASD probands from the Simons Simplex Collection in Iossifov et al., 2014. Exome sequencing of 2157 cases with intellectual disability or developmental delay in Yang et al., 2016 identified seven proband-patient trios with de novo AHDC1 variants; probands typically presented with developmental delay, intellectual disability, absent or limited speech, hypotonia, dysmorphic features, brain abnormalities, failure to thrive/feeding difficulties, and ataxia/gait abnormalities, and two of the seven probands were additionally diagnosed with autism based on DSM-IV or DSM-V criteria.
Krishnan Probability Score
Score 0.48935682110503
Ranking 6504/25841 scored genes
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ExAC Score
Score 0.99943144781763
Ranking 960/18225 scored genes
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Iossifov Probability Score
Score 0.975
Ranking 50/239 scored genes
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Sanders TADA Score
Score 0.46465407393228
Ranking 378/18665 scored genes
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Zhang D Score
Score 0.26241890795117
Ranking 3300/20870 scored genes
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