Xp11.3CNV Type: Deletion-Duplication
Largest CNV size: 664901 bp
Statistics Box:
Number of Reports: 19
Number of Reports: 19
Summary Information
Summary statement in development
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
Structural variation of chromosomes in autism spectrum disorder.
Duplication
Deletion of MAOA and MAOB in a male patient causes severe developmental delay, intermittent hypotonia and stereotypical hand movements.
Deletion
Functional impact of global rare copy number variation in autism spectrum disorders.
Duplication
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabili...
Duplication
MAOA/B deletion syndrome in male siblings with severe developmental delay and sudden loss of muscle tonus.
Deletion
Array-CGH Analysis in a Cohort of Phenotypically Well-Characterized Individuals with Essential Autism Spectrum Disorders.
Duplication
The utility of DNA methylation signatures in directing genome sequencing workflow: Kabuki syndrome and CDK13-related disorder
Duplication
Cross-Disorder Analysis of Genic and Regulatory Copy Number Variations in Bipolar Disorder
Deletion
Minor Reports
Title
Author, Year
Report Class
CNV Type
Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism.
Deletion-Duplication
The clinical utility of molecular karyotyping using high-resolution array-comparative genomic hybridization.
Deletion
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
Deletion-Duplication
Identification of candidate intergenic risk loci in autism spectrum disorder.
Duplication
Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes.
Duplication
Performance of case-control rare copy number variation annotation in classification of autism.
Duplication
Recurrent copy number variations as risk factors for Autism Spectrum Disorders: analysis of the clinical implications.
Duplication
Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights.
Deletion
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
engchuan_15_ASD_discovery_cases
Samples from the Autism Genome Project (AGP)
1892
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
N/A
85.78% Male
212362
0
2
2
kaminsky_11_DD/ID/ASD_discovery_cases
Cases from the International Standards for Cytogenomic Arrays (ISCA) consortium
15749
Unexplained developmental delay, intellectual disability, dysmorphic features, multiple congenital anomalies, autism spectrum disorders, or clinical features suggestive of a chromosomal syndrome
NA
NA
1081794
0
8
8
krumm_15_ASD_discovery_cases
Probands from the Simons Simplex Collection
2377
Diagnosis of ASD
N/A
N/A
10267
0
1
1
kushima_18_ASD_discovery_cases
Individuals predominantly recruited from the middle of Honshu Island (Japan)
1108
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.
Median age, 19 years
78.0% Male
1900362
1
0
1
kushima_22_ASD_discovery_cases
Japanese ASD probands evaluated for copy number variation from an initial cohort of 1,236 probands before quality control.
1205
Cases diagnosed with autism spectrum disorder (ASD) according to DSM-5 criteria.
Median age, 19 yrs.
77.6% Male
1900363
1
0
1
lionel_13_ASD/ADHD/DD/ID_discovery_cases
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
89985
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.)
N/A
N/A
53420
0
2
2
marshall_08_ASD_discovery_cases
Cohort of ASD families (237 simplex, 189 mulitplex) recruited from the Hospital for Sick Children, McMaster Univ., Memorial Univ., and other sites
427
ASD
664901
0
1
1
marwaha_22_DD/ID_discovery_cases
Individual with a clinical working diagnosis of Kabuki syndrome with a maternally-inherited Xp11.3 duplication affecting the KDM6A gene
1
Case presented with developmental delay and seizures
9 yrs.
Male
8001
0
1
1
miyake_23_ASD_discovery_cases
Cohort of ASD probands consisting of 351 trios, 24 quads, and two quintets included in a multi-center cohort.
405
Cases were clinically diagnosed with ASD based on DSM-V.
NA
69.88% Male
971125
1
0
1
napoli_17_ASD_discovery_cases
Children recruited between June 2009 and December 2014 at the Child Neuopsychiatry Unit of Bambino Gesu Children's Hospital, IRCCS, Rome, Italy
133
Inclusion criteria included a clinical diagnosis of pervasive developmental disorders (PDD) and of ASD, according to DSM-IV-TR and DSM-5 criteria, respectively, and fewer than six dysmorphic features (children with six or more minor anomalies and/or systemic congenital malformations, such as congenital heart defects, were excluded). Cognitive or developmental level was assessed by the brief intelligence quotient (IQ) from Leiter-R or by the general quotient (GQ) from Griffiths Mental Development Scales Extended Revised for age 2-8, GMDS-ER 2-8 (mean IQ, 73.7 24.3). The calibrated severity score (CSS) index was also calculated to quantify autism symptoms independently (median score of 7, r
Mean, 6.7 3.0 years
84.96% Male
377000
0
1
1
oikonomakis_16_ASD_discovery_cases
ASD cases evaluated with chromosomal microarray (CMA) from 2008-2015
195
Cases assessed for ASD according to DSM-IV behavioral criteria
Range, 1-38 yrs.
64.61% Male
180000
0
1
1
pinto_10_ASD_discovery_cases
Autism Genome Project (AGP) consortium patient cohort from families with at least two ASD individuals
996
ASD (ADI-R and ADOS): strict, broad, or spectrum ASD
36986
0
1
1
prasad_12_ASD_discovery_cases
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).
676
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS
NA
82.84% Male
412785
3
2
5
saito_13_ASD_discovery_cases
Affected male siblings born to healthy parents presenting with ASD, severe developmental delay and sudden loss of muscle tone
2
Diagnosis of ASD (n=1) and PDD-NOS (n=1) based on fulfillment of DSM-IV criteria
Range, 4-5 yrs.
Male
800000
2
0
2
sanchis_juan_23_ASD/DD/ID_discovery_cases
Individuals affected with a neurodevelopmental disorder (NDD) from the National Institute for Health and Care Research (NIHR) BioResource project.
489
73% (357/489) of the participants in this study had autism spectrum disorder (ASD), developmental delay (DD), intellectual disability (ID), a movement disorder or dystonia, and/or seizures.
NA
NA
386574
1
0
1
sanders_11_ASD_discovery_cases
Autistic probands from the Simons Simplex Collection (SSC). 872 probands in quartet families, 272 probands in trios.
1124
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)
Mean, 9.1 yrs.
86.1% Male
27207
5
2
7
tzetis_12_DD/ID_discovery_cases
Patients referred for aCGH analysis from 2008-present
334
Cases presented with at least one of the following clinical indications: developmental delay (DD), intellectual disability (ID), dysmorphic features, unique or multiple congenital anomalies (MCA), growth disorder, behavior disorder, and/or autism (ASD)
Range, 1 month-38 years (median age of 4 years)
560000
1
0
1
walker_13_ASD_discovery_cases
Unrelated ASD probands previously described in Lionel et al., 2011 and Pinto et al., 2010 CNV reports
1491
Diagnosis of ASD based on gold-standard instruments including ADI and ADOS.
N/A
N/A
412998
0
1
1
whibley_10_DD_discovery_cases
Two affected brothers born to healthy non-consanguienous Caucasian couple with healthy older sister
2
Severe developmental delay, intermittent hypotonia, and autistic behaviors (stereotypical hand movements)
Range, 5-15 yrs.
Male
240000
2
0
2
Controls
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
engchuan_15_ASD_discovery_controls
Platform-matched controls from three large studies: SAGE (Study of Addiction Genetics and Environment), Ontario Colorectal Cancer study, and HABC (Health Aging and Body Composition)
2342
Controls; subjects had no previous psychiatric history
N/A
46.67% Male
468617
0
2
2
kaminsky_11_DD/ID/ASD_discovery_controls
Controls from the International Standards for Cytogenomic Arrays (ISCA) consortium
10118
Controls
NA
NA
NA
NA
NA
NA
krumm_15_ASD_discovery_controls
Unaffected siblings from quad families from the Simons Simplex Collection
1786
Control
N/A
N/A
199353
0
1
1
kushima_18_ASD/SCZ_discovery_controls
Individuals selected from the general population and predominantly recruited from the middle of Honshu Island (Japan)
2095
Controls had no history of mental disorders based upon responses to questionnaires or self-reporting.
Median age, 37 years
52.0% Male
0
0
0
0
kushima_22_ASD/BPD/SCZ_discovery_controls
Psychiatrically normal control individuals selected from the general population evaluated for copy number variation from an initial cohort of 2,713 control individuals before quality control.
2671
Controls were psychiatrically normal and had no history of mental disorders based on responses to questionnaires or self-reporting.
Median age, 36 yrs.
47.8% Male
0
0
0
0
marshall_08_ASD_discovery_controls_1
German PopGen project and entries from Database of Genomic Variants
500
Controls
0
0
0
0
marshall_08_ASD_discovery_controls_2
Non-disease controls from Ontario population
1152
Controls
0
0
0
0
prasad_12_ASD_discovery_controls
PDx controls [1000 DNA samples from reportedly healthy donors (50.2% male) from BioServe (Beltsville, MD)] and 4139 in-house controls previously reported in Krawcak et al. 2006, Stewart et al. 2009, and Bierut et al. 2010. CNVs identified in controls were used to define rare ASD-specific CNVs.
5139
Control
NA
NA (PDx controls 50.2% male)
412785
0
0
0
sanders_11_ASD_discovery_controls
Matched siblings of autistic probands from the Simons Simplex Collection (SSC).
872
Controls
Mean, 10.0 yrs.
27235
3
4
7
walker_13_ASD_discovery_controls
Control samples from the SAGE cohort (n=1287), from the Ottawa Heart Institute (n=1234), and from the POPGEN collection (n=1123)
3644
Control
N/A
N/A
412998
N/A
N/A
N/A
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
engchuan_15_ASD_discovery_cases
Caucasian
Solid phase hybridization
Illumina 1M
None
kaminsky_11_DD/ID/ASD_discovery_cases
NA
aCGH
Agilent 44K, Agilent 105K
Feature Extraction, DNA Analytics
FISH, qPCR, MLPA, aCGH, standard G-banded chromosome analysis
krumm_15_ASD_discovery_cases
N/A
WES
CoNIFER, XHMM
Solid phase hybridization (Illumina 1M, 1 M Duo, or Omni 2.5)
kushima_18_ASD_discovery_cases
Japanese
aCGH
NimbleGen 720K, Agilent 400K
FASST2
Nexus Copy Number v.9.0
N/A
kushima_22_ASD_discovery_cases
Japan
aCGH
NimbleGen 720K Whole-Genome Tiling, Agilent SurePrint G3 Human CGH 400K
Fast Adaptive States Segmentation Technique 2
BioDiscovery Nexus Copy Number v.9.0
qRT-PCR
lionel_13_ASD/ADHD/DD/ID_discovery_cases
N/A
aCGH, array SNP, solid phase hybridization
Multiple platforms (Agilent, Affymetrix, Illumina)
None
marshall_08_ASD_discovery_cases
90% European, 4.5% European-mixed, 4.5% Asian, 0.07% African
Array SNP, karotyping
Affymetrix 500K
dChip, CNAG, GEMCA
qPCR, qmPCR
marwaha_22_DD/ID_discovery_cases
European
WGS
NA
miyake_23_ASD_discovery_cases
Japan
Exome sequencing
Illumina HiSeq 2000/2500
NA
XHMM
qPCR
napoli_17_ASD_discovery_cases
Italy
aCGH
Agilent Human Genome 4x180K
ADM-2
Feature Extraction v.10.5, Agilent Genomic Workbench Lite Edition v.7.4
RT-PCR
oikonomakis_16_ASD_discovery_cases
Greece
aCGH
Agilent 244K, 4x180K, or 4x180K (SurePrint G3 arrays)
None
pinto_10_ASD_discovery_cases
European
Solid phase hybridization
Illumina Infinium 1M SNP microarray
QuantiSNP, iPattern
qPCR, long-range PCR (LR-PCR), MLPA, FISH, aCGH (Agilent 1M), array SNP (Affymetrix 500K)
prasad_12_ASD_discovery_cases
Canada
aCGH
Agilent 1M
ADM-2, DNAcopy (R Bioconductor)
DNA Analytics v4.0.85 (Agilent), DNAcopy
None
saito_13_ASD_discovery_cases
Japanese
aCGH
Agilent 180K
CGH-Analytics V3.4
qPCR
sanchis_juan_23_ASD/DD/ID_discovery_cases
United Kingdom
Short-read WGS
Illumina HiSeq 2500/Illumina HiSeq X
Canvas v.1.1.0.5, Manta v.0.23.15
None
sanders_11_ASD_discovery_cases
White non-Hispanic, 74.5%; mixed, 9.3%, Asian, 4.3%, White Hispanic, 4.0%, African-American, 3.8%; other, 4.2&
Solid phase hybridization
Illumina 1M v1, Illumina 1M v3
PennCNV, QuantiSNP, GNOSIS
tzetis_12_DD/ID_discovery_cases
Greece
aCGH
Agilent 244K, Agilent 4x180K
ADM-1
Agilent Feature Extraction V9.1, Agilent CGH Analytics V4.0, Illumina GenomeStudio V2011.1
None
walker_13_ASD_discovery_cases
N/A
Array SNP, solid phase hybridization
Illumina 1M, Affymetrix 6.0
QuantiSNP, PennCNV, Birdsuite, iPattern, Affymetrix Genotyping Console
None
whibley_10_DD_discovery_cases
Caucasian
aCGH
X-chromosome-specific Nimblegen 385K array
ADM-1
Agilent CGH Analytics V3.4
Array SNP (Affymetrix 250K Nsp), FISH, qPCR, long-range PCR
Controls
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
engchuan_15_ASD_discovery_controls
Caucasian
Solid phase hybridization
Illumina 1M
None
kaminsky_11_DD/ID/ASD_discovery_controls
NA
aCGH
Agilent 44K, Agilent 105K
Feature Extraction, DNA Analytics
krumm_15_ASD_discovery_controls
N/A
WES
CoNIFER, XHMM
Solid phase hybridization (Illumina 1M, 1 M Duo, or Omni 2.5)
kushima_18_ASD/SCZ_discovery_controls
Japanese
aCGH
NimbleGen 720K, Agilent 400K
FASST2
Nexus Copy Number v.9.0
N/A
kushima_22_ASD/BPD/SCZ_discovery_controls
Japan
aCGH
NimbleGen 720K Whole-Genome Tiling, Agilent SurePrint G3 Human CGH 400K
Fast Adaptive States Segmentation Technique 2
BioDiscovery Nexus Copy Number v.9.0
qRT-PCR
marshall_08_ASD_discovery_controls_1
European
Array SNP, karotyping
Affymetrix 500K
dChip, CNAG, GEMCA
marshall_08_ASD_discovery_controls_2
European
Array SNP, karotyping
Affymetrix 500K
dChip, CNAG, GEMCA
prasad_12_ASD_discovery_controls
NA
aCGH
Agilent 1M
ADM-2, DNAcopy (R Bioconductor)
DNA Analytics v4.0.85 (Agilent), DNAcopy
sanders_11_ASD_discovery_controls
Solid phase hybridization
Illumina 1M v1 or Illumina 1M v3
PennCNV, QuantiSNP, GNOSIS
walker_13_ASD_discovery_controls
N/A
Array SNP, solid phase hybridization
Illumina 1M, Affymetrix 6.0
QuantiSNP, PennCNV, Birdsuite, iPattern, Affymetrix Genotyping Console
None
Cases
Patient ID
Author, Year
Age
Gender
Primary Diagnosis
Clinical Profile
Cognitive Profile
CNV Start
CNV End
CNV Size
Genome Build
Type Method
Validation
engchuan_15_ASD_discovery_cases-case3240_3
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
44962513
45174875
212363
GRCh38
Duplication
No
engchuan_15_ASD_discovery_cases-case5007_3
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
46511595
46548580
36986
GRCh38
Duplication
No
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001846
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
46156693
46636156
479464
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001872
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
46184889
46582592
397704
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002271
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
46456409
46476928
20520
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002438
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
46508077
46548482
40406
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002722
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
46617620
46973582
355963
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004897
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
46456409
46476928
20520
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004916
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
46514093
46548482
34390
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00005379
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
43573663
44655459
1081797
GRCh38
Duplication
Yes
krumm_15_ASD_discovery_cases-case11109.p1
N/A
Female
ASD
Proband from the Simons Simplex Collection (SSC). Family type: Trio
46462747
46473014
10268
GRCh38
Duplication
Yes
kushima_18_ASD_discovery_cases-caseASD1059
44 yrs.
F
ASD
No additional clinical information reported for this individual. Family history: unknown.
44209146
46109507
1900362
GRCh38
Deletion
N/A
kushima_22_ASD_discovery_cases-caseASD1059
NA
NA
ASD
Diagnosis of ASD according to DSM-5 criteria.
44209145
46109507
1900363
GRCh38
Deletion
Yes
lionel_13_ASD/ADHD/DD/ID_discovery_cases-case9
N/A
M
Developmental delay and anxiety disorder
Developmental delay, anxiety disorder, macrocephaly.
44334346
44387765
53420
GRCh38
Triplication
No
marshall_08_ASD_discovery_cases-NA0100-000
NA
M
ASD
NA
NA
44780400
45445301
664902
GRCh38
Duplication
Yes
marwaha_22_DD/ID_discovery_cases-case1
9 yrs.
M
Developmental delay and seizures
Clinical working diagnosis of Kabuki syndrome, congenital hyperinsulinism, global developmental delay, postnatal growth retardation, hypotonia in infancy, cortical visual impairment, seizures, severe gastroesophageal reflux requiring G-tube feeding, remote bilateral matrix hemorrhages on brain MRI, renal cysts, high arched palate, pectus excavatum, scoliosis; this patient was born to non-consanguineous parents of British and Bulgarian ancestry.
44958755
44966755
8001
GRCh38
Duplication
Yes
miyake_23_ASD_discovery_cases-case22119
NA
F
ASD
Case clinically diagnosed with ASD based on DSM-V criteria.
44229671
45200795
971125
GRCh38
Deletion
Yes
napoli_17_ASD_discovery_cases-case22
N/A
M
ASD
Case diagnosed with ASD according to DSM-5 criteria. Congenital anomalies: none. Dysmorphic features: fewer than six. Karyotype: 46,XY
44941786
45319135
377350
GRCh38
Duplication
Yes
oikonomakis_16_ASD_discovery_cases-case342
5 yrs.
M
ASD
Case was assessed for ASD according to DSM-IV behavioral criteria. Clinical characteristics other than ASD: echolalia, stereotypic movements. Note: CNV start and end points extracted from report are incomplete and do not correlate with gene (MAOA) in Table 1.
43573288
3580109
180000
NCBI36
Duplication
No
pinto_10_ASD_discovery_cases-case5007_3
NA
M
Autism
Anxiety, language delay, no epilepsy, no dysmorphic features
Below average IQ
46511595
46548580
36986
GRCh38
Duplication
Yes
prasad_12_ASD_discovery_cases-case47607
NA
M
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. CNV identified by previous SNP microarray study
46247933
46295289
47357
Unknown
Duplication
No
prasad_12_ASD_discovery_cases-case58294L
NA
M
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. Novel CNV
44380414
44386744
6331
Unknown
Deletion
No
prasad_12_ASD_discovery_cases-case70106L
NA
M
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. CNV identified by previous SNP microarray study
44803831
45216615
412785
Unknown
Duplication
No
prasad_12_ASD_discovery_cases-case96241
NA
M
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. Novel CNV
47251534
47263177
11644
Unknown
Deletion
No
prasad_12_ASD_discovery_cases-caseL656
NA
M
ASD
Diagnosis of ASD based on meeting criteria on ADI-R and/or ADOS. Novel CNV
44861727
44894573
32847
Unknown
Deletion
No
saito_13_ASD_discovery_cases-case1
5 yrs.
M
ASD
Diagnosis of ASD based on fulfilling DSM-IV criteria. Birth/neonatal history: born at 39 weeks of gestation with low birth weight for gestational age (2426 g); phototherapy provided for neonatal jaundice. Developmental milestones: sudden loss of muscle tone at 4-18 months of age; sitting on own around 13 months; no meaningful words at 3 years of age; walking with support at 4 years of age. Langauge and communication evaluation: Several meaningful words at 5 years of age. Motor and musculoskeletal evaluation: Capable of walking several meters by himself at 5 years of age. Beahvioral/psychiatric evaluation: at 3 years of age, patient did not make eye contact, had little interest in other people, and was attached to spinning toys and shiny things; no stereotypic hand movements; hand flapping and lip smacking; abnormal and self-injurious behavior (which included head-banging, hand chewing, and scratching himself) after waking; abnormal behavior disappeared at 3 years of age following risperidone treatment. Sleep disturbances: disturbed sleep patterns observed around 13 months (repeated sleeping for half an hour at a time and screaming during waking); sleep disturbances disappeared at 3 years of age following risperidone treatment. EEG: normal. Brain imaging: normal brain MRI. Other features: elevated CSF serotonin levels. Dysmorphic features: polydactyly of right thumb (operated on at 14 months), bilateral cryptorchidism (operated on at 2 years), long eyelashes, thin upper lip, intermittent internal strabismus. Growth parameters: weight of 15.0 kg (-1.3 SD) and height of 93.7 cm (-3.5 SD) at 5 years of age. Family history: younger male sibling (saito_13_ASD_discovery_cases-case2) with PDD-NOS, severe developmental delay, and sudden loss of muscle tone; healthy parents (mother with heterozygous Xp11.3 deletion is unaffected).
Severe developmental delay
43140751
43940754
800004
GRCh38
Deletion
Yes
saito_13_ASD_discovery_cases-case2
4 yrs.
M
PDD-NOS
Diagnosis of PDD-NOS based on fulfilling DSM-IV criteria. Birth/neonatal history: born at 38 weeks of gestation with birth weight normal for gestational age (2750 g). Developmental milestones: frequent loss of muscle tone around 7 months of age; unassisted sitting at 1 year; some eye gaze but no verbal or non-verbal methods to express requests at 2 years. Langauge and communication evaluation: Spoke some meaningful words. Motor and musculoskeletal evaluation: capable of standing with support. Behavioral/psychiatric evaluation: self-injurious and lip-smacking behaviors; no stereotypic hand movements. Sleep disturbances: none. EEG: unremarkable. Brain imaging: unremarkable brain MRI. Other features: elevated CSF serotonin levels; risperidone treatment started at 3 years of age. Dysmorphic features: bilateral cryptorchidism, long eyelashes, thin upper lip, intermittent strabismus. Growth parameters: weight of 13.2 kg (-1.0 SD) and height of 87.7 cm (-2.9 SD) at 4 years of age. Family history: older male sibling (saito_13_ASD_discovery_cases-case1) with ASD, severe developmental delay, and sudden loss of muscle tone; healthy parents (mother with heterozygous Xp11.3 deletion is unaffected).
Severe developmental delay
43140751
43940754
800004
GRCh38
Deletion
Yes
sanchis_juan_23_ASD/DD/ID_discovery_cases-caseG011510
NA
M
Brain structural abnormality
Patient was of European ancestry and presented with abnormality of the cerebellum.
45108465
45495038
386574
GRCh38
Deletion
No
sanders_11_ASD_discovery_cases-11109.p1
4.5
F
Autism
NA
Full-scale IQ, 86; non-verbal IQ, 96; verbal IQ 71
46458899
46476574
17676
GRCh38
Duplication
No
sanders_11_ASD_discovery_cases-11558.p1
7.4
M
Autism
NA
Full-scale IQ, 94; non-verbal IQ, 100; verbal IQ, 89
47471692
47474107
2416
GRCh38
Deletion
No
sanders_11_ASD_discovery_cases-11857.p1
6.7
M
Autism
NA
Full-scale IQ, 99; non-verbal IQ, 101; verbal IQ, 96
47471692
47474107
2416
GRCh38
Deletion
No
sanders_11_ASD_discovery_cases-12543.p1
8.9
M
ASD
NA
Full-scale IQ, 86; non-verbal IQ, 99; verbal IQ, 67
42905490
42932697
27208
GRCh38
Deletion
No
sanders_11_ASD_discovery_cases-12621.p1
5.8
M
Autism
NA
Full-scale IQ, 113; non-verbal IQ, 120; verbal IQ, 96
47471692
47474107
2416
GRCh38
Deletion
No
sanders_11_ASD_discovery_cases-12851.p1
4.7
M
Autism
NA
Full-scale IQ, 37; non-verbal IQ, 49; verbal IQ, 14
42905490
42932697
27208
GRCh38
Deletion
No
sanders_11_ASD_discovery_cases-13023.p1
4.3
F
Autism
NA
Full-scale IQ, 115; non-verbal IQ, 118; verbal IQ, 106
44442415
44445096
2682
GRCh38
Duplication
No
tzetis_12_DD/ID_discovery_cases-case61
M
DD/ID
Mild dysmorphic features, hypotonia, severe speech delay
43463947
44021580
557634
GRCh38
Deletion
No
walker_13_ASD_discovery_cases-case3-0100-000
N/A
M
ASD
N/A
N/A
45060991
45473988
412998
GRCh38
Duplication
No
whibley_10_DD_discovery_cases-caseIV:2
5 yrs.
M
Developmental delay
Patient died unexpectedly at 5 years of age. Birth/neonatal history: born by normal delivery with birth weight of 2.38 kg at about 36 weeks of gestation after normal pregnancy; neonatal hypotonia and feeding difficulties, which required tube feeding, noted; several attacks of sudden hypotonia in first 6 months, which continued in spite of phenobarbital and sodium valproate treatment (started at 9 months of age). Developmental milestones: significantly delayed development; sitting at 20 months, walking with support at 2 years 6 months. Motor and musculoskeletal evaluation: no independent walking achieved at time of death. Behavioral/psychiatric evaluation: recurrent screaming episodes with head banging and hand flapping; additional behaviors of head scratching and hand chewing. EEG: short-wave activity in occipital area noted following onset of hypotonic episodes. Brain imaging: CT scan following onset of hypotonic episodes showed widening of the ventricles and basal spaces. Other features: following patient's death, autopsy did not reveal any abnormalities of internal organs except for brain, which was mildly underweight and showed small foci of perivascular calcification, occasional haemosiderin granules in the Virchow-Robin spaces, and loss of cerebellar Purkinje cells and some cortical neurons. Dysmorphic features: inner canthal folds, long eyelashes, extra upper lateral incisor, unusual hair whorl on posterior hairline. Growth parameters: weight <3rd %ile, lenght <3rd %ile, and OFC 3rd-10th %ile at 4 years of age. Family history: born to healthy non-consanguineous Caucasian parents; healthy older sister; affected brother with similar phenotype (severe developmental delay, intermittent hypotonia, etc.).
Severe developmental delay
43682038
43922394
240357
GRCh38
Deletion
Yes
whibley_10_DD_discovery_cases-caseIV:3
15 yrs.
M
Developmental delay
Birth/neonatal history: born by vertex delivery at 38 weeks gestation after normal pregnancy and weighed 2.5 kg; noted to have jerky movements when falling asleep or walking up; episodes of sudden profound hypotonia (definite axial hypotonia at 13 weeks). Developmental milestones: sitting at 15 months, bottom shuffling at 2 years 8 months, independent walking at 4 years. Language and communication evaluation: able to communicate with many single words and British sign language. Motor and musculoskeletal evaluation: independent walking, clumsy running, continued episodes of hypotonia. Behavioral/psychiatric evaluation: early-onset pursuing and smacking of lips, development of writhing hand movements from 10 months; patient enjoys social events and company. EEG: recent EEG performed during a hypotonic episode showed no focal signs or paroxysmal features. Brain imaging: brain MRI revealed no abnormalities. Other features: lamotrigine treatment tried between 6 and 8 years of age; initial decrease in episode frequency and subsequent increase to 20-30 times/day led to stop of treatment. Dysmorphic features: inner canthal folds, long eyelashes, intermittent convergent strabismus. Growth parameters: height 0.4th %ile, weight 25th %ile, and OFC 3rd-10th %ile at 15 years of age. Family history: born to healthy non-consanguineous Caucasian parents; healthy older sister; affected brother with similar phenotype (severe developmental delay, intermittent hypotonia, etc.) who died unexpectedly at age fo 5 years.
Severe developmental delay
43682038
43922394
240357
GRCh38
Deletion
Yes
Controls
Patient ID
Author, Year
Age
Gender
Primary Diagnosis
Clinical Profile
Cognitive Profile
CNV Start
CNV End
CNV Size
Genome Build
Type Method
Validation
engchuan_15_ASD_discovery_controls-controlB746449_1007844499
N/A
N/A
Control
No previous psychiatric history
45129175
45597792
468618
GRCh38
Duplication
No
engchuan_15_ASD_discovery_controls-controlHABC_900337_900337
N/A
N/A
Control
No previous psychiatric history
46499154
46548580
49427
GRCh38
Duplication
No
krumm_15_ASD_discovery_controls-control14172.s1
N/A
Female
Control
Unaffected sibling from the Simons Simplex Collection (SSC)
44343517
44542870
199354
GRCh38
Duplication
Yes
sanders_11_ASD_discovery_controls-11064.s1
10
F
Control (matched sibling)
NA
NA
44442415
44445096
2682
GRCh38
Duplication
No
sanders_11_ASD_discovery_controls-11198.s1
8.8
F
Control (matched sibling)
NA
NA
44442415
44445096
2682
GRCh38
Duplication
No
sanders_11_ASD_discovery_controls-11694.s1
6.6
F
Control (matched sibling)
NA
NA
44322283
44346751
24469
GRCh38
Duplication
No
sanders_11_ASD_discovery_controls-11839.s1
4
F
Control (matched sibling)
NA
NA
43762162
43767234
5073
GRCh38
Deletion
No
sanders_11_ASD_discovery_controls-12063.s1
11.8
F
Control (matched sibling)
NA
NA
44442415
44445096
2682
GRCh38
Duplication
No
sanders_11_ASD_discovery_controls-12162.s1
11
F
Control (matched sibling)
NA
NA
44169676
44196911
27236
GRCh38
Deletion
No
sanders_11_ASD_discovery_controls-12650.s1
4.7
F
Control (matched sibling)
NA
NA
47471692
47474107
2416
GRCh38
Deletion
No
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
engchuan_15_ASD_discovery_cases-case3240_3
Unknown
KDM6A
engchuan_15_ASD_discovery_cases-case5007_3
Unknown
RNU6-50P,ZNF674-AS1,ZNF674
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001846
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
ACTBP1,LINC01186,GAPDHP65,RNU6-50P,MKI67P1,KRBOX4,ZNF674-AS1,CHST7,ZNF674,SLC9A7
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001872
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Paternal
Unknown
Unknown
ACTBP1,LINC01186,GAPDHP65,RNU6-50P,MKI67P1,KRBOX4,ZNF674-AS1,CHST7,ZNF674
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002271
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
KRBOX4
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002438
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
RNU6-50P,ZNF674-AS1,ZNF674
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002722
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Paternal
Unknown
Unknown
PGAM1P7,YBX1P8,RP2,LINC01545,SLC9A7,JADE3
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004897
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
KRBOX4
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004916
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
RNU6-50P,ZNF674-AS1,ZNF674
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00005379
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
RRM2P3,FDPSP5,CHTF8P1,RPL19P20,MAOA,NDP,NDP-AS1,TATDN2P1,FUNDC1,MAOB,EFHC2
krumm_15_ASD_discovery_cases-case11109.p1
Illumina 1M
Paternal
Simplex
Segregated
KRBOX4
kushima_18_ASD_discovery_cases-caseASD1059
While a subset of CNVs were reported to have been validated by qPCR in the report, precisely which CNVs were validated was not reported
Unknown
Unknown
Unknown
RRM2P3,FDPSP5,CHTF8P1,RPL19P20,RPSAP61,RN7SL291P,DUSP21,KRT8P14,MIR221,MIR222,LINC02595,MED28P4,KRT18P68,PCNAP3,TATDN2P1,FUNDC1,MIR222HG,EFHC2,LINC01204,KDM6A
kushima_22_ASD_discovery_cases-caseASD1059
qRT-PCR
Unknown
FDPSP5,DUSP21,DIPK2B,EFHC2,KRT18P68,FUNDC1,PLLPP1,KRT8P14,RPL19P20,PCNAP3,MFFP3,LINC02595,MIR222,MIR221,RPSAP61,CHTF8P1,MED28P4,SRSF6P1,TATDN2P1,RRM2P3,LINC01204,MIR222HG,RN7SL291P,KDM6A
lionel_13_ASD/ADHD/DD/ID_discovery_cases-case9
Unknown
EFHC2
marshall_08_ASD_discovery_cases-NA0100-000
qPCR, qmPCR
Unknown
NA
NA
DUSP21,KDM6A
marwaha_22_DD/ID_discovery_cases-case1
MLPA
Maternal
Simplex
KDM6A
miyake_23_ASD_discovery_cases-case22119
qPCR
De novo
FDPSP5,DUSP21,DIPK2B,EFHC2,FUNDC1,RPL19P20,RPSAP61,CHTF8P1,TATDN2P1,RRM2P3,RN7SL291P,KDM6A
napoli_17_ASD_discovery_cases-case22
RT-PCR
Maternal
KDM6A
oikonomakis_16_ASD_discovery_cases-case342
Unknown
MAOB (intronic)
pinto_10_ASD_discovery_cases-case5007_3
qPCR-Maternal,Agilent1M
maternal
Multiplex
Not segregated
RNU6-50P,ZNF674-AS1,ZNF674
prasad_12_ASD_discovery_cases-case47607
Unknown
Unknown
Unknown
ZNF674,LOC401588
prasad_12_ASD_discovery_cases-case58294L
Unknown
Simplex
Unknown
0 genes
prasad_12_ASD_discovery_cases-case70106L
Unknown
Unknown
Unknown
CXorf36,KDM6A
prasad_12_ASD_discovery_cases-case96241
Unknown
Unknown
Unknown
0 genes
prasad_12_ASD_discovery_cases-caseL656
Unknown
Unknown
Unknown
CXorf36
saito_13_ASD_discovery_cases-case1
qPCR
Maternal
Multiplex
Segregated
IMPDH1P4,NANOGP10,PINCR,MAOA,MAOB
saito_13_ASD_discovery_cases-case2
qPCR
Maternal
Multiplex
Segregated
IMPDH1P4,NANOGP10,PINCR,MAOA,MAOB
sanchis_juan_23_ASD/DD/ID_discovery_cases-caseG011510
Unknown
Simplex
DIPK2B,PLLPP1,KDM6A
sanders_11_ASD_discovery_cases-11109.p1
Paternal
Simplex (quad-proband unmatched)
Unknown
KRBOX4
sanders_11_ASD_discovery_cases-11558.p1
Maternal
Simplex (quad-proband unmatched)
Unknown
ZNF41
sanders_11_ASD_discovery_cases-11857.p1
Maternal
Simplex (quad-proband matched)
Segregated
ZNF41
sanders_11_ASD_discovery_cases-12543.p1
Maternal
Simplex (trio)
NA
sanders_11_ASD_discovery_cases-12621.p1
Maternal
Simplex (quad-proband matched)
Not segregated
ZNF41
sanders_11_ASD_discovery_cases-12851.p1
Maternal
Simplex (quad-proband matched)
Not segregated
sanders_11_ASD_discovery_cases-13023.p1
Paternal
Simplex (quad-proband matched)
Not segregated
tzetis_12_DD/ID_discovery_cases-case61
Maternal
Unknown
MAOA,NDP,NDP-AS1,MAOB
walker_13_ASD_discovery_cases-case3-0100-000
Unknown
Simplex
Unknown
KDM6A
whibley_10_DD_discovery_cases-caseIV:2
Array SNP (Affymetrix 250K Nsp), FISH, qPCR, long-range PCR
Maternal
Multiplex
Segregated
MAOA,MAOB
whibley_10_DD_discovery_cases-caseIV:3
Array SNP (Affymetrix 250K Nsp), FISH, qPCR, long-range PCR
Maternal
Multiplex
Segregated
MAOA,MAOB
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
engchuan_15_ASD_discovery_controls-controlB746449_1007844499
Unknown
LINC01204
engchuan_15_ASD_discovery_controls-controlHABC_900337_900337
Unknown
RNU6-50P,ZNF674-AS1,ZNF674
krumm_15_ASD_discovery_controls-control14172.s1
Omni2.5-4v1
Paternal
FDPSP5,FUNDC1,EFHC2
sanders_11_ASD_discovery_controls-11064.s1
Maternal
Simplex (quad)
NA
sanders_11_ASD_discovery_controls-11198.s1
Paternal
Simplex (quad)
NA
sanders_11_ASD_discovery_controls-11694.s1
Paternal
Simplex (quad)
NA
EFHC2
sanders_11_ASD_discovery_controls-11839.s1
Paternal
Simplex (quad)
NA
MAOB
sanders_11_ASD_discovery_controls-12063.s1
Both parents
Simplex (quad)
NA
sanders_11_ASD_discovery_controls-12162.s1
Paternal
Simplex (quad)
NA
EFHC2
sanders_11_ASD_discovery_controls-12650.s1
Both parents
Simplex (quad)
NA
ZNF41
No Animal Model Data Available