3q29

Description:

Proband carrying a novel familial 3q29 deletion centromeric to the 3q29 deletion region that segregated with psychiatric disorders (schizophrenia, major depression, anxiety disorder, personality disorder) in the proband's family

Diagnosis:

Proband diagnosed with severe autism accompanied with cognitive delay at age of 30 months after evaluation with ADOS module 1 (communication score 9, reciprocal social interaction score 12), CARS (score of 39), and VABS (age-equivalent score of 20 months versus chronological age of 4 years).

CNV Size: 1360000

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Affected individuals from MSSNG cohort (1395 cases from 1187 families) and the Simons Simplex 2 (SSC2) cohort (584 cases from simplex quad families)

Diagnosis:

Cases diagnosed with ASD

CNV Size: 432716

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Patient, born to healthy non-consanguineous parents with no family history of ID, referred at 18 months of age for marked psychomotor and developmental delay; patient carries balanced de novo triple translocation t(11;17;19)(q13.3;q25.1;q13.42)dn with breakpoint disrupting the SHANK2 gene.

Diagnosis:

Severe DD/ID, language impairment, behavioral abnormalities

CNV Size: 124355

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Patients referred to clinical genetics service and recruited for CMA application study

Diagnosis:

Developmental delay/intellectual disability (DD/ID), autism (ASD), and/or multiple congenital anomalies (MCA)

CNV Size: 1560000

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Male patient, fourth of five child born at term gestation to healthy non-consanguineous parents.

Diagnosis:

ASD (diagnosis criteria unknown). Additional diagnosis of ADHD (inattentive type), diagnosis tools unknown.

CNV Size: 1300000

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Autistic cases from Autism Genetic Research Exchange (AGRE)

Diagnosis:

ASD: diagnosis confirmed through ADI and in some cases ADOS-G. 17 cases with syndromic autism (autism and less than common craniofacial dysmorphology, limb or digit abnormality, or ocular abnormality), 19 cases selected at random with autism and no associated syndromic features

CNV Size: 247667

Deletion: 2

Duplication: 0

Total CNV: 2

Description:

Proband from simplex family recruited and assessed by Autism Center of Excellence (ACE) at the University of Illinois-Chicago

Diagnosis:

Diagnosis of autistic disorder at 43 months of age. Diagnostic evaluation performed using ADI-R and ADOS-WPS module 3. Additional measures: Repetitve Behavior Scale-Revised (RBS-R) and Aberrant Behavior Checklist-Community Version (ABC-CV) for repetitive behaviors; Social Communication Questionnaire (SCQ) & Social Responsiveness Scale (SRS) for social interactions; Clinical Evaluation of Language Fundamentals (CELF) for language ability; Wechsler Abbreviated Scale of Intelligence (WASI) for verbal and nonverbal abilities; Vineland Adaptive Behavior Scales (VABS-II) for adaptive functioning.

CNV Size: 133344

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

Patients with 3q29 microdeletions recruited in two different Italian research and care hospitals: IRCCS Oasi Maria Santissima, Troina, and IRCCS Carlo Besta, Milan.

Diagnosis:

All four patients met DSM-IV-TR criteria for intellectual disability (ID); cognitive performances assessed using Wechsler Intelligence Scale for Children (WISC-III) or Leiter International Performace Scale -Revised (LIPS-R). One patient with additional comorbidity of PDD-NOS; behavioral performances assessed using Children Behavior Check List (CBCL), adaptive performances assessed using Vineland Behavior Adaptive Scale (VABS).

CNV Size: 1607314

Deletion: 4

Duplication: 0

Total CNV: 4

Description:

Primarily pediatric cases with intellectual disability, developmental delay, and/or ASD (cohort consists of 13,318 previously unpublished cases and 15,767 cases originally published in Cooper et al., Nature Genetics 2011); annotated CNVs extracted from Table 1 ("New CNVs") and Supplementary Table 2 ("Newly Significant Genomic Disorders").

Diagnosis:

Intellectual disability, developmental delay, and/or ASD

CNV Size: 1740000

Deletion: 11

Duplication: 6

Total CNV: 17

Description:

Discovery case samples derived from AGRE set 4 (most recent patient recruitment)

Diagnosis:

Idiopathic autism; cases designated as 'spectrum' and 'not quite autism' excluded, as were cases with known genetic syndromes or other non-idiopathic causes

CNV Size: 149164

Deletion: 0

Duplication: 2

Total CNV: 2

Description:

Replication case samples derived from AGRE sets 1-3

Diagnosis:

Idiopathic autism; cases designated as 'spectrum' and 'not quite autism' excluded, as were cases with known genetic syndromes or other non-idiopathic causes

CNV Size: 134366

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

ASD probands from 457 families (418 simplex, 39 multiplex) from the SPARK cohort

Diagnosis:

All cases diagnosed with ASD

CNV Size: 22133

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

Children seen from 2007 to 2010 at Univ. of South Alabama Autism Diagnostic Clinic

Diagnosis:

Autism spectrum disorder (ASD; diagnosis made using DSM-IV criteria & AODS) and/or global developmental delay; cases evaluated for craniofacial dysmorphism

CNV Size: NA

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

ASD cases with sporadic autism from the Simons Simplex Collection (SSC)

Diagnosis:

Diagnosis of ASD based on meeting criteria on ADOS, ADI-R, and expert clinical judgment. 246 cases with no intellectual disability, 90 cases with intellectual disability. Exclusion criteria: significant hearing, vision, or motor problems; significant birth complications; a diagnosis of ASD-related disorders, such as Fragile X; or having a relative (up to 3rd degree) with ASD or sibling showing ASD-related symptoms.

CNV Size: 119071

Deletion: 22

Duplication: 19

Total CNV: 41

Description:

Samples from affected children submitted to Signature Genomic Laboratories from 2008-2010.

Diagnosis:

Developmental delay with or without congenital malformations

CNV Size: 1610000

Deletion: 20

Duplication: 18

Total CNV: 38

Description:

ASD-affected individuals referred to the Children Development and Behavior Research Center (CDRBC) at Harbin Medical University, China, between January 2007 and June 2011.

Diagnosis:

Diagnosis of ASD made using Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS)

CNV Size: 51156

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

1979 simplex cases from the Simons Simplex Collection (SSC), 579 multiplex cases from AGRE.

Diagnosis:

Diagnosis of ASD based on meeting criteria on the Autism Diagnostic Observation Schedule (ADOS) and on the Autism Diagnostic Interview, Revised (ADI-R)

CNV Size: 2153582

Deletion: 2

Duplication: 3

Total CNV: 5

Description:

Data from individuals with developmental delay derived from two published reports (Cooper et al., 2011 & Kaminsky et al., 2011)

Diagnosis:

Developmental delay

CNV Size: 2153582

Deletion: 6

Duplication: 0

Total CNV: 6

Description:

Children with autism ascertained from the Childhood Autism Risks from Genetics and Environment (CHARGE) study conducted through the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute at UC-Davis after passing QC criteria (274 initial cases)

Diagnosis:

Diagnosis of autism confirmed by ADOS and ADI-R. Exclusion criteria: children with developmental delay but lacking symptoms and autism, as well as children with ASD as defined by the CHARGE protocol

CNV Size: 97905

Deletion: 10

Duplication: 25

Total CNV: 35

Description:

Patients with 16q24.2 deletions recruited at the University of Alberta, Edmonton, the Hospital for Sick Children, Toronto, Signature Genomic Laboratories, and the Mayo Clinic).

Diagnosis:

22 patients with ASD (19 with pervasive developmental delay/PDD, 3 with autism), 3 patients with intellectual disability (defined as IQ<70 by DSM-IV); 11 patients with facial dysmorphisms.

CNV Size: 455116

Deletion: 0

Duplication: 2

Total CNV: 2

Description:

Patients receiving a diagnosis of ASD in the Department of Child Health Care, Children's Hospital of Fudan University, that were included consecutively from January 2019 to December 2020.

Diagnosis:

Cases met criteria for autism spectrum disorder (ASD) using DSM-5 criteria.

CNV Size: 1524042

Deletion: 2

Duplication: 0

Total CNV: 2

Description:

Cases from the International Standards for Cytogenomic Arrays (ISCA) consortium

Diagnosis:

Unexplained developmental delay, intellectual disability, dysmorphic features, multiple congenital anomalies, autism spectrum disorders, or clinical features suggestive of a chromosomal syndrome

CNV Size: 4203614

Deletion: 10

Duplication: 15

Total CNV: 25

Description:

Cypriot patients with ASD or autistic features

Diagnosis:

Children with preliminary diagnosis of ASD [reevaluated by clinical geneticist to rule out autistic-like syndromes and retested for ASD based on DSM-IV-TR and ICD-10 using Gilliam Autism Rating Scale-2 (GARS-2)]

CNV Size: 1070000

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Autistic cases from an initial sample of 83 Finnish families comprising 257 family members following quality control

Diagnosis:

Diagnosis of ASD based on DSM-IV, 4th edition, or ICD-10 criteria; patients screened based on Childhood Autism Rating Scale (CARS), Asperger Syndrome Screening Questionnaire, and Asperger's Syndrome Diagnostic Interview.

CNV Size: 94065

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

Probands from quad families ascertained as part of the Simons Simplex Collection (SSC); CNVs detected using data from four previously published exome sequencing studies (O'Roak et al., 2011; Iossifov et al., 2012; O'Roak et al., 2012; Sanders et al., 2012)

Diagnosis:

Diagnosis of ASD. Social Responsiveness Scale (SRS) used as a quantitative measure of social deficits

CNV Size: 1494502

Deletion: 2

Duplication: 1

Total CNV: 3

Description:

Probands from the Simons Simplex Collection

Diagnosis:

Diagnosis of ASD

CNV Size: 1074625

Deletion: 4

Duplication: 3

Total CNV: 7

Description:

Individuals predominantly recruited from the middle of Honshu Island (Japan)

Diagnosis:

Cases were diagnosed with ASD according to DSM-5 criteria, with diagnostic and screening instruments (ADI-R, ADOS, ASQ, and SRS) used to evaluate ASD-related behaviors and symptoms in the majority of cases.

CNV Size: 1692142

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

Individuals predominantly recruited from the middle of Honshu Island (Japan)

Diagnosis:

Cases were diagnosed with schizophrenia (SCZ) according to DSM-5 criteria.

CNV Size: 1627239

Deletion: 3

Duplication: 0

Total CNV: 3

Description:

Japanese ASD probands evaluated for copy number variation from an initial cohort of 1,236 probands before quality control.

Diagnosis:

Cases diagnosed with autism spectrum disorder (ASD) according to DSM-5 criteria.

CNV Size: 1692143

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

Japanese schizophrenia probands evaluated for copy number variation from an initial cohort of 3,111 probands before quality control.

Diagnosis:

Cases diagnosed with schizophrenia (SCZ) according to DSM-5 criteria.

CNV Size: 2040881

Deletion: 4

Duplication: 0

Total CNV: 4

Description:

Autistic probands from 887 families from the Simons Simplex Collection (SSC)

Diagnosis:

ASD

CNV Size: 1630060

Deletion: 1

Duplication: 1

Total CNV: 2

Description:

Epilepsy patients collected at four French hospitals from 2009: Strasbourg Univ. Hospital (n=40), Lyons Univ. Hospital (n=18), Henri Gastaut Hospital (St. Paul Centre) in Marseille (n=2), and Reims American Memorial Hospital (n=1).

Diagnosis:

Epilepsy/epileptic encephalopathy. 41 patients with continuous spike and wave during slow-wave sleep syndrome (CSWSS), 20 patients with Landau-Kleffner syndrome (LKS). 12 (out of 57) patients displayed autistic features; ADHD features (hyperactivity, attention deficit and/or aggressiveness) reported in 41/58 patients,

CNV Size: 514000

Deletion: 0

Duplication: 3

Total CNV: 3

Description:

Individuals referred for postnatal genetic testing across 10 different sites, including 64,114 subjects with neurodevelopmental disorders, from Alberta Children's Hospital, BBGRE, Boston Children's Hospital, Credit Valley Hospital, the Hospital for Sick Children, Italian diagnostic laboratories, The Mayo Clinic, Odense University Hospital, Signature Genomics, and The Centre for Applied Genomics

Diagnosis:

64,114 cases with neurodevelopmental disorders (including ASD, ADHD, developmental delay, and/or intellectual disability); 25,871 cases with non-neurodevelopmental disorders (multiple congential anomalies, etc.)

CNV Size: 1672701

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Children affected with ASD from 1,464 families from the Autism Genetic Resource Exchange (AGRE)

Diagnosis:

Diagnosis according to ADOS and ADI-R

CNV Size: 500000

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

Study participants in the PAGES cohort, a large ongoing population-based cohort study in Sweden that started in 2012 with the overall aim to identify possible genetic and environmental risk factors for ASD.

Diagnosis:

Cases diagnosed with ASD according to ICD-9 and ICD-10 criteria.

CNV Size: 1612058

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

SCZ probands of Ashkenazi Jewish descent recruited nationally over a 6-year period

Diagnosis:

Diagnosis of schizophrenia based on meeting DSM-IV citeria

CNV Size: 846088

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Subjects recruited in the Centre de Reference deficiences intellectuelles de causes rares', the 'Centre Diagnostic Autisme', Pitie-Salpetriere Hospital (Paris, France) or the Fondation Lejeune over a period of 3 years (20092011).

Diagnosis:

Cases assessed with ADI-R

CNV Size: 1594000

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Autism Genome Project (AGP) consortium patient cohort from families with at least two ASD individuals

Diagnosis:

ASD (ADI-R and ADOS): strict, broad, or spectrum ASD

CNV Size: 350489

Deletion: 1

Duplication: 2

Total CNV: 3

Description:

ASD probands from simplex and multiplex families collected as part of stage 2 of the Autism Genome Project (AGP) after quality control (1,604 before QC)

Diagnosis:

Cases classified according to ADOS and ADI-R

CNV Size: 1704322

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Patients with 15q11.2 CNVs assessed in the Child and Adolescent Neuropsychiatry Unit of Campus Bio-Medico University Hospital in Rome, Italy, from an original cohort of 243 subjects affected by neurodevelopmental disorders and their first-degree relatives

Diagnosis:

Neuropsychiatric diagnosis made according to DSM-IV criteria. Instruments used for data collection were Leiter International Performance Scale-Revised (Leiter-R), Wechsler Intelligence Scale for Children-3rd Revision (WISC III), Wechsler Adult Intelligence Scale-3rd edition (WAIS-III), Autism Diagnostic Observation Schedule (ADOS), Autism and Asperger Diagnostic Scale-Revised (RAADS-R), Autism Diagnostic Interview-Revised (ADI-R), Vineland Adaptive Behavior Scales (VABS), and the Child Behavior Checklist (CBCL/6-18)

CNV Size: 53687

Deletion: 0

Duplication: 3

Total CNV: 3

Description:

ASD cases of European ancestry from AGRE retained after filtering (original cohort size of 432 cases)

Diagnosis:

Cases diagnosed with ASD

CNV Size: 163625

Deletion: 0

Duplication: 4

Total CNV: 4

Description:

Unrelated ASD cases recruited from three Canadian sites (Hospital for Sick Children, McMaster University, and Memorial University of Newfoundland); the majority of cases had been previously genotyped with results published in Marshall et al., 2008 and Pinto et al., 2010. 20 cases from initial cohort of 696 were excluded from further analysis (due to CNVs > 5 Mb).

Diagnosis:

Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS

CNV Size: 701745

Deletion: 4

Duplication: 4

Total CNV: 8

Description:

Samples submitted between 3/2004 and 7/2008 that had ASD as indication for study (Signature Genomic Labs, Spokane, WA)

Diagnosis:

ASD

CNV Size: 2438912

Deletion: 1

Duplication: 1

Total CNV: 2

Description:

Two patients (one Caucasian female, one Hispanic male) with 3q29 microdeletions

Diagnosis:

Autism, mental retardation/intellectual disability, & psychiatric symptoms

CNV Size: 2100000

Deletion: 2

Duplication: 0

Total CNV: 2

Description:

Patient with 3q29 deletion from the Simons Simplex Collection previousy described in Sanders et al. 2011 CNV report (sanders_11_ASD_discovery_cases-11079.p1)

Diagnosis:

Diagnosis of autism based on meeting criteria on ADOS and ADI-R following enrollment in SSC study at age of 12 years (previous diagnosis of PDD-NOS at age of 4 years); additional diagnoses of intellectual disability (FSIQ of 53 on DAS) and childhood psychosis.

CNV Size: 1580000

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Individuals with severe congenital brain malformations [agenesis of the corpus callosum (ACC), cerebellar hypoplasia (CBLH), and/or polymicrogyria (PMG)] and additional neurodevelopmental phenotypes

Diagnosis:

Diagnosis of agenesis of the corpus callosum (ACC), cerebellar hypoplasia (CBLH), and/or polymicrogyria (PMG); additional diagnoses of autism spectrum disorder (ASD), developmental delay (DD), intellectual disability (ID) and/or seizures in some patients

CNV Size: 135371

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

Consecutive patients referred with either ASD or learning disability for genetic services at the University of Kansas Medical Center from 2009-2012

Diagnosis:

ASD (n=65) or learning disability (LD; n=150); learning disability defined as developmental delay (infants & children) and/or intellectual disability (older children & adults)

CNV Size: 1700000

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Epilepsy patients recruited as part of a multi-center effort from Austria, Germany, Australia, and Canada; 98 patients from multiplex families (at least two affected siblings)

Diagnosis:

Cases diagnosed with rolandic epilepsy according to International Classification of Seizures and Epilepsies; 230 cases with rolandic epilepsy, 51 cases with atypical rolandic epilepsy.

CNV Size: 636000

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

Galician (NW Spain) patients recruited from the Complexo Hospitalario Universitario de Santiago de Compostela and referred to the Fundacion Publica Galega de Medicina Xenomica for genetic study

Diagnosis:

All participants had a clinical diagnosis of idiopathic intellectual disability (ID) or global developmental delay (DD) with or without another medical condition [e.g. autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), epilepsy, dysmorphic features, and/or congenital anomalies]

CNV Size: 1666108

Deletion: 1

Duplication: 2

Total CNV: 3

Description:

Autistic probands from the Simons Simplex Collection (SSC). 872 probands in quartet families, 272 probands in trios.

Diagnosis:

ASD diagnosis: 89.5% autism; 8.5% PDD-NOS, 2% Asperger syndrome. Mean full-scale IQ 85.1 1.5 (mean verbal IQ, 81.9 1.7; mean non-verbal IQ, 88.4 1.4)

CNV Size: 1689956

Deletion: 55

Duplication: 9

Total CNV: 64

Description:

Patients from original discovery case cohort that were subsequently used in chromosomal microarray analysis (CMA). Original discovery case cohort (n=933) was 80.9 % male and consisted of 461 patients recruited through Autism Consortium (AC) & 472 patients added through samples from Children's Hospital Boston DNA Diagnostic laboratory (CHB).

Diagnosis:

ASD (initial case cohort of 933 cases consisted of 447 patients diagnosed with autistic disorder, 454 with PDD-NOS, 31 with Asperger disorder, and 1 with CDD. AC Cohort: 54 patients with secondary diagnosis of mental retardation, 36 with seizures, and 16 with multiple congenital anomalies)

CNV Size: 453000

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

Patients selected for aCGH studies between 2005 and 2007 at Human Genetics Laboratory at Univ. of Nebraska

Diagnosis:

Primary indication noted on request form of autism. 54 patients with simple (non-syndromic) autism, 14 patients with complex (syndromic) autism.

CNV Size: NA

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Unrelated ASD cases from Canada (Hospital for Sick Children, McMaster University, Memorial University of Newfoundland, University of Alberta, and Montral Children's Hospital of McGill University Health Centre) and Europe (PARIS and specialized clincial centers in France, Sweden, Germany, Finland, and the UK).

Diagnosis:

Diagnosis of ASD based on Autism Diagnostic Interview-Revised (ADI-R) and/or Autism Diagnostic Observation Schedule (ADOS). In some ASD cases from Sweden, the Diagnostic Interview for Social and Communication Disorders (DISCO-10) was applied instead of ADI-R.

CNV Size: 126226

Deletion: 0

Duplication: 2

Total CNV: 2

Description:

Patient referred to genetics clinic (Dept. of Genetics & Laboratory Medicine, Credit Valley Hospital, Ontario, Canada) for non-syndromic speech delay

Diagnosis:

Developmental delay (non-syndromic significant speech delay). Differential diagnosis of ASD ruled out by psychiatric assessment at 3.5 yrs., but no specific diagnosis suggested.

CNV Size: 37500

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

ASD probands from 22 families (20 trios, 1 quad with two affected siblings, and 1 quad with an affected proband and his unaffected fraternal twin) with recent shared ancestry that were recruited either from Jordan or from the Dallas/Fort Worth area.

Diagnosis:

Cases diagnosed with ASD based on standard autism diagnostic measures (ADOS, ADI-R, DSM-V)

CNV Size: 1620789

Deletion: 2

Duplication: 0

Total CNV: 2

Description:

Discovery cohort of Canadian individuals with ASD

Diagnosis:

ASD

CNV Size: 126226

Deletion: 0

Duplication: 1

Total CNV: 1

Description:

Individuals with BPD from Belgium, individuals with BPD originating from a geographically isolated population of the County of Vasterbotten (Northern Sweden), and Northwestern European individuals with BPD contacted through inpatient and outpatient services of hospitals in Aberdeen and Edinbergh, Scotland.

Diagnosis:

Bipolar disorder (BPD). Final diagnosis based on meeting DSM-IV criteria.

CNV Size: 0

Deletion: 0

Duplication: 0

Total CNV: 0

Description:

Patients recruited through specific psychiatric service in Scotland serving the needs of patients with ID who also suffer from behavioral disorders.

Diagnosis:

Intellectual disability (ID). Cases with total IQ<70 met definition of ID.

CNV Size: 0

Deletion: 0

Duplication: 0

Total CNV: 0

Description:

Northwestern European individuals with MDD contacted through inpatient and outpatient services of hospitals in Aberdeen and Edinbergh, Scotland.

Diagnosis:

Major depressive disorder (MDD). Final diagnosis based on meeting DSM-IV criteria.

CNV Size: 0

Deletion: 0

Duplication: 0

Total CNV: 0

Description:

Individuals with SCZ from Belgium, individuals with SCZ originating from a geographically isolated population of the County of Vasterbotten (Northern Sweden), and Northwestern European individuals with SCZ contacted through inpatient and outpatient services of hospitals in Aberdeen and Edinbergh, Scotland.

Diagnosis:

Schizophrenia (SCZ). Final diagnosis based on meeting DSM-IV criteria.

CNV Size: 197000

Deletion: 2

Duplication: 0

Total CNV: 2

Description:

Discovery cohort of ASD cases recruited from the Department of Psychiatry of National Taiwan University Hospital (NTUH), Chang Gung Memorial Hospital (CGMH), Taoyuan, and Taoyuan Mental Hospital (TMH), Taiwan.

Diagnosis:

Cases diagnosed with autistic disorder according to DSM-IV and confirmed by using the Chinese version of ADI-R. Cases' autistic behaviors assessed by Social Responsiveness Scale (SRS), and cognitive functions assessed by the Weschler Intelligence Scale for Children-Third Edition (WISC-III) and the Wisconsin Card Sorting Test (WCST).

CNV Size: 147893

Deletion: 0

Duplication: 2

Total CNV: 2

Description:

Patients referred to the Duke Autism Genetics Clinic for clinical genetic evaluation of ASD and DD/ID from 2010-2014

Diagnosis:

66 cases with confirmed primary diagnosis of ASD (DSM-IV, DSM-5, ADOS, and ADI-R used to support ASD diagnosis), 49 cases with primary diagnosis of DD or ID (based on IQ and DQ scores).

CNV Size: 5701000

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

ASD genomes (1745 ASD probands, 879 ASD-affected siblings, 1 ASD-affected father, and 1 ASD-affected grandfather) from AGRE (n=730), the AGRE; Autism Treatment Network cohort (n=192) ,the ASD: Genomes to Outcomes Study cohort (n=1421), the Baby Siblings Research Consortium (n=43), the Baby Siblings Research Consortium; The Autism Simplex Collection cohort (n=6), the Infant Sibling Study (n=62), th

Diagnosis:

ASD diagnosis of research quality when meeting criteria on one (n=437) or both (n=1361) of the diagnostic measures ADI-R and ADOS; clinical diagnosis of ASD (n=819) when given by expert clinician according to DSM-IV or DSM-5

CNV Size: 1708000

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

ASD probands from 353 pedigrees (338 simplex trios, 15 multiplex families) recruited from the Department of Child and Adolescent Psychiatry, Shanghai Mental Health Center (Shanghai, China).

Diagnosis:

Cases diagnosed with ASD using DSM-IV.

CNV Size: 1519762

Deletion: 1

Duplication: 0

Total CNV: 1

Description:

Patients diagnosed with ASD from the the Department of Psychiatry, Beijing Children's Hospital, from July 2019 to May 2021.

Diagnosis:

Cases diagnosed with autism spectrum disorder (ASD) according to DSM-V criteria; the two most common features of ASD cases in this cohort were intellectual disability and language delay.

CNV Size: 2222430

Deletion: 1

Duplication: 0

Total CNV: 1

Clinical Profile:

Proband diagnosed with severe autism accompanied with cognitive delay at age of 30 months after evaluation with ADOS module 1 (communication score 9, reciprocal social interaction score 12), CARS (score of 39), and VABS (age-equivalent score of 20 months versus chronological age of 4 years). Birth/neonatal history: pregnancy reported as normal, with exception of a positive Wald test; normal fetal karyotype (46,XX); born by spontaneous delivery at term; birth weight of 3120 g (25th %ile), length of 50 cm (50th %ile), and OFC of 35 cm (75th %ile); Apgar scores 9/10; suffered from GERD and milk protein intolerance since first months of life. Developmental milestones: reached motor milestones within expected range (independent walking at 14 months); initially referred for langauge delay at age of 30 months. EEG: normal. Brain imaging: normal brain MRI. Behavioral/psychiatric evaluation: motor stereotypies and bruxism at last clinical evaluation (age of 9 years), selective eating with no hyperphagia, nocturnal awakenings, occasional self-injuries. Gastrointestinal evaluation: constipation. Dysmorphic features: acanthosis nigricans on neck and armpits, otherwise no evident facial dysmorphisms. Growth parameters: infantile obesity (weight of 53 kg, height of 138 cm, BMI of 27.8) at age of 9 years; normal growth pattern during initial clincial examination at age of 30 months [weight of 14 kg (50th %ile), height of 95 cm (50th %ile), OFC of 48.5 cm (25th %ile)]. Family history: family history remarkable for psychiatric and ophthalmologic disorders that segregate with the 3q29 deletion in this pedigree; proband's mother (III-6) with history of anxiety disorder, major depression, and obesity; two maternal aunts and a brother of the maternal grandmother (individuals III-4, III-5, and II-3 in this family) were institutionalized for schizophrenia; anxiety disorder reported in maternal great-grandmother (I-2); subject III-1 in this family with ASD, social anxiety, and borderline personality disorder; subject II-2 with dysthymia, avoidant personality disorder, and microcephaly; learning disabilities reported for subjects II-3 and III-4; deletion non-carriers III-2 and III-3 had no history of cognitive and psychiatric disorder.

Cognitive Profile:

Severe cognitive delay (Griffith scale total quotient=34) at last clinical evaluation (age of 9 years)

Primary Disorder Inheritence: Maternal

Family Profile: Multi-generational

Clinical Profile:

Patient referred at 18 months for marked psychomotor and developmental delay. Karyotype: 46, XY, t(11;17;19)(q13.3;q25.1;q13.42)dn; translocation with breakpoints within the SHANK2 and UBE2O genes. Birth/neonatal history: duing pregnancy mother had cervical cancer (treated after birth), born at 39 weeks gestation by C-section; birth weight -0.23 SD, length -0.83 SD, OFC +0.7 SD; uneventful perinatal adaption; ventricular septal defect diagnosed at 2 months. Developmental milestones: psychomotor retardation noted at 1.5 years; sat independently at 8 months, began to walk with support at 2.5 years, independent walking at 3.5 years, not toilet trained at 5 years of age. Language and communication evaluation: no spoken language. Motor and musculoskeletal evaluation: ataxia, able to stand with support. Behavioral/psychiatric evaluation: anxious, exhibited habit disorder with stereotypic movements, decreased sensitivity to pain, often caused self-injury. EEG: increased irregular activity. Brain imaging: normal by ultrasound. Visual and auditory evaluation: normal. Sleep disturbances: serious sleeping disturbances. Other features: elevated alkaline phosphatase, lactate dehydrogenase, and serum magnesium levels. Dysmorphic features: coarse face with facial dysmorphism, broad thorax, clinodactyly of 2nd and 3rd toes. Growth parameters: weight of 19.3 kg (+0.1 SD), length of 105 cm (-1.0 SD) and OFC of 51 cm (0 SD) at 5 years of age. Family history: second child of healthy non-consanguineous parents; no family history of miscarriages, ID, or alcohol exposure in utero.

Cognitive Profile:

Severe DD/ID. Evaluation at age of 1.5 years: Brunet-Lezine development test showed delay in movements, coordination, communication, and social skills; psychomotor development corresponded to 9 months, development quotient of 48; Bayley Scales of Infant Development gave Developmental Index score of 84.

Primary Disorder Inheritence: -

Family Profile: Possibly simplex (no info on 1st child)

Clinical Profile:

Developmental delay

Cognitive Profile:

Developmental delay

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

Children Behavioral Check List (CBCL) results (score above 64 equals index of behavioral problems): internalizing, 91; externalizing, 84; total, 66. Vineland Adaptive Behavior Scale (VABS) results (years): communication, 10.0; daily living skills, 9.2; socialization, 10.4; total, 10.0. Birth/neonatal history: delivery at pregnancy week 40; birth weight of 2.850 kg (10th %ile), birth length of 49 cm. Developmental milestones: steady head holding at 3 months, sitting alone at 6 months, walking at 12 months, babbling at 12 months, first word at 15 months. Behavioral/psychiatric evaluation: exhibited both internalizing behaviors (such as withdrawal, anxiety/depression, thought problems) and externalizing behaviors (such as social problems and aggressive behavior) on CBCL test. Skeletal abnormalities and chest wall deformities: brachycephaly and pectus carinatum. EEG: normal. Cardiac defects: none. Ocular abnormalities: yes (not specified). Additional features: joint hyperlaxity; REED nevus. Dysmorphic features: high nasal bridge, large posteriorly rotated ears, long narrow face, high palate. Growth parameters: current weight 75th %ile, current height 75th %ile.

Cognitive Profile:

Mild intellectual disability; IQ score of 63 (WISC-III), similar verbal IQ and performance IQ scores; mainstream school education with support

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

Children Behavioral Check List (CBCL) results (score above 64 equals index of behavioral problems): internalizing, 71; externalizing, 67; total, 71. Vineland Adaptive Behavior Scale (VABS) results (years): communication, 7.0; daily living skills, 6.4; socialization, 5.9; total, 6.4. Birth/neonatal history: delivery at pregnancy week 39; birth weight of 3.250 kg (50th %ile), birth length of 50 cm. Developmental milestones: steady head holding at 3 months, sitting alone at 6 months, walking at 13 months, babbling at 8 months, first word at 12 months. Behavioral/psychiatric evaluation: exhibited both internalizing behaviors (such as withdrawal, anxiety/depression, thought problems) and externalizing behaviors (such as social problems and aggressive behavior) on CBCL test. Skeletal abnormalities and chest wall deformities: brachycephaly and kyphosis. EEG: spikes of right frontal region. Cardiac defects: none. Ocular abnormalities: yes (not specified). Additional features: nasal voice. Dysmorphic features: high nasal bridge, short philtrum, large posteriorly rotated ears, clinodactyly, widely spaced teeth. Growth parameters: current weight 3rd-10th %ile, current height 10th %ile.

Cognitive Profile:

Moderate intellectual disability; IQ score of 48 (WISC-III), verbal IQ score significantly lower than performance IQ score; mainstream school education with support

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

Children Behavioral Check List (CBCL) results (score above 64 equals index of behavioral problems): internalizing, 58; externalizing, 53; total, 59. Vineland Adaptive Behavior Scale (VABS) results (years): communication, 5.11; daily living skills, 3.6; socialization, 2.8; total, 3.8. Birth/neonatal history: delivery at pregnancy week 41; birth weight of 2.735 kg (10th %ile), birth length of 47 cm. Developmental milestones: steady head holding at 3 months, sitting alone at 7 months, walking at 15 months, babbling at 8 months, first word at 14 months with subsequent language regression. Behavioral/psychiatric evaluation: exhibited both internalizing behaviors (such as withdrawal, anxiety/depression, thought problems) and externalizing behaviors (such as social problems and aggressive behavior) on CBCL test; patient also showed inattention, repetitive and poorly consistent language production and impaired social interaction suggestive of PDD-NOS. Skeletal abnormalities and chest wall deformities: kyphosis, early closure of fontanelle, pectus carinatum. EEG: poor organization, high amplitude, occasional sequences of slow activity, occasional generalized epileptiform discharges. Cardiac defects: patent foramen ovale. Ocular abnormalities: slight photophobia, ocular fundus, slightly pale optic disc. Additional features: episodes of tremor at birth, possibly due to hypocalcemia; intestinal subocclusion due to Mesenterium Commune; joint hyperlaxity, horseshoe kidney. Dysmorphic features: high nasal bridge, microcephaly, short philtrum, large posteriorly rotated ears, clinodactyly, long narrow face, hypospadias. Growth parameters: current weight 10th-25th %ile, current height 10th-25th %ile.

Cognitive Profile:

Severe intellectual disability; IQ score of 37 (LIPS-R); mainstream school education with support

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

Children Behavioral Check List (CBCL) results (score above 64 equals index of behavioral problems): internalizing, 76; externalizing, 66; total, 73. Vineland Adaptive Behavior Scale (VABS) results (years): communication, 4.3; daily living skills, 2.6; socialization, <1.6; total, 2.8. Birth/neonatal history: delivery at pregnancy week 39; birth weight of 2.200 kg (<3rd %ile), birth length of 47 cm. Developmental milestones: steady head holding at 3 months, sitting alone at 6 months, walking at 17 months, babbling at 9 months, first word at 12 months. Behavioral/psychiatric evaluation: exhibited both internalizing behaviors (such as withdrawal, anxiety/depression, thought problems) and externalizing behaviors (such as social problems and aggressive behavior) on CBCL test; patient had psychotic outburst at age of 8 years; behavior characterized by withdrawal, irritability and oppositive behaviors, poor tolerance of frustration and anxiety, emotional dysregulation with rapid feelings change and non-contextual laughter, stereotyped behavior, immediate echolalia and repetitive and/or telegraphic, incongruent responses at time of evaluation. Skeletal abnormalities and chest wall deformities: none. EEG: normal (slight excess of fast components during sleep). Cardiac defects: none. Ocular abnormalities: yes (not specified). Additional features: slight cerebellar atrophy. Dysmorphic features: high nasal bridge, short philtrum, large posteriorly rotated ears. Growth parameters: current weight 75th %ile, current height 75th-90th %ile.

Cognitive Profile:

Severe intellectual disability; IQ score unable to be evaluated due to neuropsychiatric disorder (Raven Progressive Colored Matrices administered at age of 11 years showed IQ of 50); mainstream school education with support

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

Diagnosed with autism at 3.5 yrs (diagnosis criteria unknown). Diagnosed with ADHD predominantly inattentive type at 6 yrs. 11 mos. Speech delay. Developmental milestones: sat independently at 6.5 months; crawled at 10 months; first words at 15 months; evaluated for speech and pervasive developmental delay at ~3 yrs. Mild facial dysmorphisms: elongated face, down-slanting palpebral fissures, normally set but somewhat prominent ears, high nasal bridge with prominent tip, short but well-delineated philtrum. Ligamentous laxity. Very midly decreased general tone with notable hypermobility of fingers & hands. No gait ataxia. Digit clinodactyly (mild 5th finger bilaterally). Elongated fingers. Growth parameters: weight, 21.6 kg (45th %ile); height, 125 cm (85th %ile); head circumference, 50.5 cm (25th %ile). No family history of learning difficulties, birth defects, or mental retardation; siblings of case in good health with normal intelligence.

Cognitive Profile:

Low-average to average full-scale IQ scores. Stanford-Binet IQ scores (5 yrs.): full-scale IQ 87 (19th %ile, low average), nonverbal IQ 99 (47th%ile, average), verbal IQ 77 (6th %ile, borderline). Weschler Intelligence Scale IQ scores (6 yrs. 11 mos.): full-scale IQ 84 (14th %ile, low average). General Ability Index (GAI) 0f 94 (34th %ile, average). WRAT 4 scores (6 yrs. 11 mos.): math computation score of 80 (9th %ile, K4 grade level), word reading score of 118 (88th %ile, grade 2.8 level). Strengths noted in associative reasoning, vocabulary, spatial organization, individual word reading & sentence comprehension. Weaknesses noted in verbal formulation, working memory tasks, math computation & spelling. Initially startedin pre-school program for autistic children after ASD diagnosis, transitioned to public mainstream kindergarten at 5 yrs., currently in 1st grade with good-to-satisfactory performance in all academic areas.

Primary Disorder Inheritence: -

Family Profile: Simplex

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

N/A

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

Diagnosis: autism. Syndromic autism features: fused ribs

Cognitive Profile:

-

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

Diagnosis: autism. Syndromic autism features: fused ribs

Cognitive Profile:

-

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

Diagnosis of autistic disorder at 43 months of age. ADI-R evaluation: impairments in reciprocal social interaction, 23; qualitative abnormalities in communication, 20; restricted and repetitive patterns of behavior, 6; abnormalitiy of development evident at or before 36 months, 3. ADOS evaluation: communication, 4; social, 7; social affect, 7; restricted repetitive behaviors, 3; calibrated severity score, 6. Birth/neonatal history: 38-week gestation (birth weight 3.6 kg); feeding difficulties, generalized hypotonia, and weakness of left leg and arm noted during infancy. Developmental milestones: loss of previously normal language development at 19 months, with language loss persisting for 11 months; gross motor milestones wihtin normal limits (dragged left leg while learning to crawl). Language and communication evaluation: Clinical evaluation of language fundamentals (CELF-4), 109 (73rd %ile); Social communication questionnaire, 26; primarily verbal communication (fluent and conversational language that could be repetitive, usage of overly formal words in conservation, atypical tone and prosody); limited use of gestures and impairments in nonverbal communication. Motor and musculoskeletal evaluation: pattern of asymmetic physical development consistent with mild left hemiparesis; stretch reflexes 2+ and asymmetrical throughout; left side of face less mobile than right. Behavioral/psychiatric evaluation: Repetitive behavior scale-revised, 6; Aberrant behavior checklist-community, 27; Childhood routines inventory (version 1.2), 44; notable behavior patterns include avoidance of eye contact, staring at hands, preference for certain foods and routines, sensitivity to particular pieces of clothing, irritation by other people, conservations about limited range of topics, preference for solitary activities, talking to himself loudly, engagement in reciprocal social smiling, exhibition of limited insight into others' experiences and narrow understanding of the nature of interpersonal relationships; exhibition of multiple sensory-seeking behaviors and sensitivity to certain stimuli and loud noises. Epilepsy/seizures: no report of clinical seizure. EEG: normal at 22 months; repeat EEG at 5 years showed left temporal and frontal epileptiform waves. Brain imaging: brain MRI normal at 22 months. Growth parameters: head circumference of 56.5 cm (98th %ile; in macrocephalic range). Family history: sister with social awkwardness; father with social isolation/anxiety and elevated broader autism phenotype questionnaire aloofness score (3.75); mother reported six miscarriages and one ectopic pregnancy prior to conception of proband.

Cognitive Profile:

Vineland adaptive behavior scale, 98 (45th %ile).

Primary Disorder Inheritence: -

Family Profile: Simplex

Clinical Profile:

-

Cognitive Profile:

-

Primary Disorder Inheritence: -

Family Profile: -

Clinical Profile:

-

Cognitive Profile:

-

Primary Disorder Inheritence: -

Family Profile: -

Clinical Profile:

-

Cognitive Profile:

-

Primary Disorder Inheritence: -

Family Profile: -

Clinical Profile:

Dysmorphic features: unknown

Cognitive Profile:

IQ unknown

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

ASD; no other clinical information provided

Cognitive Profile:

N/A

Primary Disorder Inheritence: -

Family Profile: Unknown

Clinical Profile:

ADOS score: 8. Vineland composite score: 72.

Cognitive Profile:

No mental retardation/intellectual disability. Full-scale IQ, 128; Verbal IQ, 120; Non-verbal IQ, 126.

Primary Disorder Inheritence: -

Family Profile: Simplex

Clinical Profile:

ADOS score: 9. Vineland composite score: 81.

Cognitive Profile:

No mental retardation/intellectual disability. Full-scale IQ, 79; Verbal IQ, 86; Non-verbal IQ, 78.

Primary Disorder Inheritence: -

Family Profile: Simplex

Clinical Profile:

ADOS score: 6. Vineland composite score: 80.

Cognitive Profile:

No mental retardation/intellectual disability. Full-scale IQ, 106; Verbal IQ, 122; Non-verbal IQ, 95.

Primary Disorder Inheritence: -

Family Profile: Simplex

Clinical Profile:

ADOS score: 6. Vineland composite score: 68.

Cognitive Profile:

Mild mental retardation/intellectual disability. Full-scale IQ, 67; Verbal IQ, 54; Non-verbal IQ, 74.

Primary Disorder Inheritence: -

Family Profile: Simplex

Clinical Profile:

ADOS score: 9. Vineland composite score: 67.

Cognitive Profile:

Moderate mental retardation/intellectual disability. Full-scale IQ, 48; Verbal IQ, 39; Non-verbal IQ, 59.

Primary Disorder Inheritence: -

Family Profile: Simplex

Clinical Profile:

ADOS score: 10. Vineland composite score: 64.

Cognitive Profile:

No mental retardation/intellectual disability. Full-scale IQ, 75; Verbal IQ, 84; Non-verbal IQ, 71.

Primary Disorder Inheritence: -

Family Profile: Simplex

Clinical Profile:

ADOS score: 9. Vineland composite score: 69.

Cognitive Profile:

No mental retardation/intellectual disability. Full-scale IQ, 85; Verbal IQ, 80; Non-verbal IQ, 94.

Primary Disorder Inheritence: -

Family Profile: Simplex

Clinical Profile:

ADOS score: 10. Vineland composite score: 75.

Cognitive Profile:

No mental retardation/intellectual disability. Full-scale IQ, 91; Verbal IQ, 74; Non-verbal IQ, 103.

Primary Disorder Inheritence: -

Family Profile: Simplex

Clinical Profile:

ADOS score: 8. Vineland composite score: 80.

Cognitive Profile:

No mental retardation/intellectual disability. Full-scale IQ, 103; Verbal IQ, 120; Non-verbal IQ, 93.

Primary Disorder Inheritence: -

Family Profile: Simplex

Clinical Profile:

ADOS score: NA. Vineland composite score: 77.

Cognitive Profile:

No mental retardation/intellectual disability. Full-scale IQ, 109; Verbal IQ, 128; Non-verbal IQ, 97.