4q31.23CNV Type: Deletion-Duplication
Largest CNV size: 24599 bp
Statistics Box:
Number of Reports: 9
Number of Reports: 9
Summary Information
Summary statement in development
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
Cross-Disorder Analysis of Genic and Regulatory Copy Number Variations in Bipolar Disorder
Deletion
Minor Reports
Title
Author, Year
Report Class
CNV Type
Rare structural variation of synapse and neurotransmission genes in autism.
Duplication
Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism.
Deletion-Duplication
Use of array CGH to detect exonic copy number variants throughout the genome in autism families detects a novel deletion in TMLHE.
Deletion
Performance of case-control rare copy number variation annotation in classification of autism.
Deletion-Duplication
Copy number variation analysis of patients with intellectual disability from North-West Spain.
Deletion
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
celestino-soper_11_ASD_discovery_cases
ASD probands from Simons Simplex Collection (SSC) trios. 90 of the probands in this study were also used in the Sanders et al. 2011 CNV report.
99
ASD
87.88% Male
190
1
0
1
costa_21_ASD_discovery_cases
ASD probands referred to the Centro de Estudos sobre o Genoma Humano e Celulas-tronco (CEGH-CEL, Instituto de Biociencias (IB), Universidade de Sao Paulo, USP) between 2009 and 2018.
144
Cases diagnosed with ASD by psychiatrists or neurologists based on the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or DSM-5.
Range, 1-34 yrs. (mean, 7.7 yrs.)
77.08% Male
254894
1
0
1
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
262876
1
1
2
gai_11_ASD_discovery_cases
Discovery case samples derived from AGRE set 4 (most recent patient recruitment)
631
Idiopathic autism; cases designated as 'spectrum' and 'not quite autism' excluded, as were cases with known genetic syndromes or other non-idiopathic causes
86393
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
314144
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
314145
1
0
1
kushima_22_SCZ_discovery_cases
Japanese schizophrenia probands evaluated for copy number variation from an initial cohort of 3,111 probands before quality control.
3014
Cases diagnosed with schizophrenia (SCZ) according to DSM-5 criteria.
Median age, 45 yrs.
53.5% Male
28488
1
0
1
maini_18_ASD/DD/ID_discovery_cases
Patients evaluated at the Clinical Genetics Unit of Arcispedale Santa Maria Nuova, AUSL-IRCCS of Reggio Emilia that were investigated through aCGH between 2005 and 2016
293
Cases presented with one or more neurodevelopmental disorders (NDD), multiple congenital anomalies (MCA), and/or dysmorphic features. Most frequent neurodevelopmental diagnoses include language delay (78.5%), intellectual disability (66.4%), motor delay (50.7%), and ASD (13.9%); dysmorphic features were also frequently observed (52.7%)
Mean age, 7 yrs. (range, 1 mo.-29 yrs.)
57.5% Male
168000
0
1
1
quintela_17_DD/ID_discovery_cases
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
573
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]
Range, 3 months-18 years
60.38% Male
631525
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
24599
2
1
3
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
473948
1
1
2
kanduri_15_ASD_discovery_controls
Unrelated Finnish samples from the cohort of Health 2000 survey from an initial sample of 288 individuals following quality control
269
Controls screened for DSM-IV mental disorders using the Composite International Diagnostic Interview and psychotic disorders using the research version of the Structured Clinical Interview for DSM-IV
N/A
N/A
367828
1
0
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
sanders_11_ASD_discovery_controls
Matched siblings of autistic probands from the Simons Simplex Collection (SSC).
872
Controls
Mean, 10.0 yrs.
0
0
0
0
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
celestino-soper_11_ASD_discovery_cases
aCGH
Agilent 1M
ADM-2
Agilent Feature Extraction v10.7.3.1, Agilent DNA Analytics v4.0.76
None
costa_21_ASD_discovery_cases
Brazil
aCGH
Agilent 180K
NA
Agilent Genomic Workbench
aCGH (Agilent 180K)
engchuan_15_ASD_discovery_cases
Caucasian
Solid phase hybridization
Illumina 1M
None
gai_11_ASD_discovery_cases
European
Solid phase hybridization
Illumina Infinium II HumanHap550 BeadChip
BeadStudio 3.0
None
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
kushima_22_SCZ_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
maini_18_ASD/DD/ID_discovery_cases
Italian
aCGH, array SNP
Multiple platforms, including Agilent and Affymetrix arrays (8x60K oligochips since 2012)
None
quintela_17_DD/ID_discovery_cases
North West Spain
Array SNP
Affymetrix Cytogenetics Whole-Genome 2M SNP array, Affymetrix CytoScan HD
Affymetrix ChAS v.1.2.2
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
Controls
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
engchuan_15_ASD_discovery_controls
Caucasian
Solid phase hybridization
Illumina 1M
None
kanduri_15_ASD_discovery_controls
Finnish
Solid phase hybridization
Illumina Infinium HD Human610-Quad BeadChip
QuantiSNP, PennCNV
Illumina BeadStudio
None
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
sanders_11_ASD_discovery_controls
Solid phase hybridization
Illumina 1M v1 or Illumina 1M v3
PennCNV, QuantiSNP, GNOSIS
Cases
Patient ID
Author, Year
Age
Gender
Primary Diagnosis
Clinical Profile
Cognitive Profile
CNV Start
CNV End
CNV Size
Genome Build
Type Method
Validation
celestino-soper_11_ASD_discovery_cases-11076
NA
M
ASD
NA
NA
147642748
147642938
191
GRCh38
Deletion
No
costa_21_ASD_discovery_cases-caseP18
NA
M
ASD
Case diagnosed with ASD based on DSM-IV or DSM-5 criteria. Additional clinical features: echolalia.
148379261
148634154
254894
GRCh38
Deletion
Yes
engchuan_15_ASD_discovery_cases-case3032_3
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
147908006
147965445
57440
GRCh38
Deletion
No
engchuan_15_ASD_discovery_cases-case9619_201
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
147952387
148215263
262877
GRCh38
Duplication
No
gai_11_ASD_discovery_cases-AU1247301
Autism
149402824
149489216
86393
Unknown
Duplication
No
kushima_18_ASD_discovery_cases-caseASD0243
16 yrs.
F
ASD, ID, epilepsy/seizures
Developmental milestones: language delay, motor delay. Behavioral/psychiatric evaluation: sensory hypersensitivity. Epilepsy/seizures: positive for epileptic seizures/epilepsy. Family history: negative.
Intellectual disability (IQ < 70)
148159332
148473475
314144
GRCh38
Deletion
N/A
kushima_22_ASD_discovery_cases-caseASD0243
NA
NA
ASD
Diagnosis of ASD according to DSM-5 criteria.
148159331
148473475
314145
GRCh38
Deletion
Yes
kushima_22_SCZ_discovery_cases-caseSCZ3605
NA
NA
Schizophrenia
Diagnosis of schizophrenia according to DSM-5 criteria.
148251774
148280261
28488
GRCh38
Deletion
Yes
maini_18_ASD/DD/ID_discovery_cases-case2
5 yrs.
M
ASD and language delay
Birth history: born at 40 weeks gestation, no reported pregnancy anomalies. Developmental milestones: language delay. Language and communication evaluation: language disorder. Musculoskeletal evaluation: pectus excavatum, proximally placed thumbs, single palmar crease. Behavioral/psychiatric evaluation: ASD. Epilepsy/abnormal EEG: positive for epilepsy and/or abnormal EEG. Additional medical history:. Dysmorphic features: high forehead, epicanthus, tubular nose, bulbous nasal tip, anteverted nares, microstomia, microdontia, prominent and smooth ears, preauricular tag. Growth parameters: normal head circumference, normal growth. Family history: negative for consanguineity, negative for familiarity, family history negative for NDDs.
Normal (no intellectual disability or learning disorder)
147620301
147788721
168421
GRCh38
Duplication
No
quintela_17_DD/ID_discovery_cases-caseID_237
17 yrs.
M
Intellectual disability
Dysmorphic facial features
Intellectual disability
147773297
148404820
631524
GRCh38
Deletion
No
sanders_11_ASD_discovery_cases-12287.p1
7.9
M
Autism
NA
Full-scale IQ, 43; non-verbal IQ, 55; verbal IQ, 28
149164186
149186711
22526
GRCh38
Deletion
No
sanders_11_ASD_discovery_cases-12321.p1
11.2
M
Autism
NA
Full-scale IQ, 96; non-verbal IQ, 108; verbal IQ, 76
148507937
148527301
19365
GRCh38
Duplication
No
sanders_11_ASD_discovery_cases-12597.p1
6.4
M
Autism
NA
Full-scale IQ, 70; non-verbal IQ, 77; verbal IQ, 66
146803200
146827799
24600
GRCh38
Deletion
No
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-controlB883531_1007844959
N/A
N/A
Control
No previous psychiatric history
148483702
148527186
43485
GRCh38
Deletion
No
engchuan_15_ASD_discovery_controls-controlHABC_902647_902647
N/A
N/A
Control
No previous psychiatric history
149267309
149741257
473949
GRCh38
Duplication
No
kanduri_15_ASD_discovery_controls-control_split1727
N/A
N/A
Control
Control screened for DSM-IV mental disorders using the Composite International Diagnostic Interview and psychotic disorders using the research version of the Structured Clinical Interview for DSM-IV
148687610
149055437
367828
Unknown
Deletion
No
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
celestino-soper_11_ASD_discovery_cases-11076
Unknown
Simplex
NA
TMEM184C,PRMT9
costa_21_ASD_discovery_cases-caseP18
aCGH (Agilent 180K)
De novo
ASS1P8,NR3C2,RNA5SP166
engchuan_15_ASD_discovery_cases-case3032_3
Unknown
ARHGAP10
engchuan_15_ASD_discovery_cases-case9619_201
Unknown
NR3C2,ARHGAP10
gai_11_ASD_discovery_cases-AU1247301
Inherited
NR3C2
kushima_18_ASD_discovery_cases-caseASD0243
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
Simplex
Unknown
NR3C2
kushima_22_ASD_discovery_cases-caseASD0243
qRT-PCR
Unknown
NR3C2
kushima_22_SCZ_discovery_cases-caseSCZ3605
qRT-PCR
Unknown
NR3C2
maini_18_ASD/DD/ID_discovery_cases-case2
Unknown
Simplex
Unknown
RNA5SP165,MIR4799,TMEM184C,PRMT9,ARHGAP10
quintela_17_DD/ID_discovery_cases-caseID_237
Unknown
Unknown
MIR4799,RN7SL254P,NR3C2,ARHGAP10
sanders_11_ASD_discovery_cases-12287.p1
Unknown
Simplex (trio)
NA
LINC02355
sanders_11_ASD_discovery_cases-12321.p1
Paternal
Simplex (quad-proband matched)
Segregated
ASS1P8
sanders_11_ASD_discovery_cases-12597.p1
Maternal
Simplex (quad-proband matched)
Segregated
TTC29
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
engchuan_15_ASD_discovery_controls-controlB883531_1007844959
Unknown
ASS1P8
engchuan_15_ASD_discovery_controls-controlHABC_902647_902647
Unknown
LINC02355,IQCM
kanduri_15_ASD_discovery_controls-control_split1727
Unknown
ARHGAP10,NR3C2
No Animal Model Data Available