4q12-q13.1CNV Type: Duplication
Largest CNV size: 4500000 bp
Statistics Box:
Number of Reports: 3
Number of Reports: 3
Summary Information
A maternally-inherited duplication in this region was identified in a male patient with autism; the patient's mother had sub-threshold ADHD symptoms, while the patient's father, who transmitted a 5q32 deletion in the patient, had a history of speech delay, gradual hearing impairment in the past decade, and may have some autistic traits in the social reciprocity domain.
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabili...
Deletion-Duplication
Identification of two inherited copy number variants in a male with autism supports two-hit and compound heterozygosity models of autism.
Duplication
High resolution analysis of rare copy number variants in patients with autism spectrum disorder from Taiwan.
Duplication
Minor Reports
Title
Author, Year
Report Class
CNV Type
No Minor Reports
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
chen_17_ASD_discovery_cases
Patients recruited from the Children's Mental Health Center, National Taiwan University Hospital, Taipei, Taiwan and Department of Psychiatry, Chang-Gung Memorial Hospital, Kuei-Shan, Taiwan.
335
All cases met the clinical diagnosis of autistic disorder as defined by DSM-IV; diagnosis was confirmed by interviewing parents using the Chinese version of ADI-R, and all cases received further clincial evaluation according to DSM-5 diagnostic criteria for ASD. Intelligence was measured using the Wechsler Primary and Preschool Scale of Intelligence-Revised (WPPSI-R), the Wechsler Intelligence Scale for Children-3rd Edition (WISC-III), or the Wechsler Adult Intelligence Scale (WAIS). Autistic-like social deficits were assessed using the Social Responsiveness Scale (SRS); symptoms of inattention, hyperactivity, and oppositional behavior were assessed using the Swanson, Nolan and Pelham Quest
Mean age, 9.4 4.0 years
89.25% Male
4545000
0
1
1
gau_12_ASD_discovery_cases
ASD cases recruited from the Children Mental Health Center, Dept. of Psychiatry, Taiwan Univ. Hospital (Taipei, Taiwan), child psychiatric clinics of private hospitals, & special or resource education programs at schools in northern Taiwan.
315
Cases met diagnostic criteria of autistic disorder defined by DSM-IV; clinical diagnosis of autism confirmed using Chinese version of ADI-R.
Range, 3-17 yrs. (mean, 9.08 4.20)
88.25% Male
4500000
0
1
1
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
8072009
2
1
3
Controls
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
chen_17_ASD_discovery_controls1
Control subjects chosen from the Han Chinese Cell and Genome Bank (HCCGB) in Taiwan
1093
Subjects received physical check-up and questionnaire screening to ensure that they did not have any abnormal physical condition and mental illness
Mean age, 68.1 10.1 years
48.03% Male
0
0
0
0
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
sanders_11_ASD_discovery_controls
Matched siblings of autistic probands from the Simons Simplex Collection (SSC).
872
Controls
Mean, 10.0 yrs.
72550
0
1
1
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
chen_17_ASD_discovery_cases
Han Chinese
Array SNP
Affymetrix 6.0
Affymetrix Genotyping Console v.4.1
RT-qPCR
gau_12_ASD_discovery_cases
Taiwanese
Array SNP
Affymetrix 6.0
Genotyping Console 3.0.2
qPCR
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
Controls
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
chen_17_ASD_discovery_controls1
Han Chinese
Array SNP
Affymetrix 6.0
Affymetrix Genotyping Console v.4.1
kaminsky_11_DD/ID/ASD_discovery_controls
NA
aCGH
Agilent 44K, Agilent 105K
Feature Extraction, DNA Analytics
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
chen_17_ASD_discovery_cases-caseU-2075
N/A
M
ASD
Case met the clinical diagnosis of autistic disorder as defined by DSM-IV, which was confirmed by interviewing parents using the Chinese version of ADI-R; case also received further clincial evaluation according to DSM-5 diagnostic criteria for ASD. ADI-R evaluation results: Qualitative abnormalities in reciprocal social interaction, current score 17 (past score 28); Qualitative abnormalities in verbal and nonverbal communication, current score 12 (past score 18); Qualitative abnormalities in nonverbal communication, current score 4 (past score 10); Restricted, repetitive, and stereotyped patterns of behaviour, current score 8 (past score 10); Abnormality of development evident at or before 36 months, past score 5. Behavioral/psychiatric evaluation: Social Responsiveness Scale (SRS) score 82; Swanson, Nolan and Pelham Questionnaire (SNAP-IV) score 22. Epilepsy: no history of epilepsy.
Performance IQ n/a, Verbal IQ n/a, Full-scale IQ n/a
57323576
61868907
4545332
GRCh38
Duplication
Yes
gau_12_ASD_discovery_cases-case1
18 yrs.
M
Autism
Case clinically diagnosed with autistic disorder and childhood autism based on DSM-IV and ICD-10 diagnostic criteria, respectively, at 2.5 years of age. Clinical assessment and ADI-R evaluation at 16.5 years of age showed that case reached criteria for autistic disorder (autism) as defined by DSM-IV and ICD-10 (ADI-R scores: score of 28 in "qualitative abnormalities in reciprocal social interaction" area, score of 18 in "qualitative abnormalities in communication" area, and score of 10 in "restricted, repetitive, stereotyped patterns of behaviors" area). Case displayed ADHD symptoms (six items of overt inattention and one item of overt hyperactivity-impulsivity symptoms on Chinese version of Swanson, Nolan, and Pelham, version VI scale), but had sub-threshold inattention symptoms and severe functional impairment, thereby failing to meet full DSM-IV diagnostic criteria for ADHD.Developmental milestones: walked alone at 18 months; spoke 1st word other than papa/mama at 5 years; spoke 1st sentence after 10 years. Lanaguage and communication evaluation: language primarily used to express basic needs and not for communication. Behavioral/psychiatric evaluation: non-meaningful verbal outputs, some echolaila, lack of social reciprocity, no direct gaze, no response to verbal stimuli or gestures meant to catach attention, restricted & stereotyped behaviors & activities; high level of hyperactivity, impulsivity, inattention since age of 3 years and lasting until junior high (case had never taken medication to treat these ADHD symptoms). Family history: only child of unrelated parents who did not demonstrate any obvious autistic symptoms or DSM-IV psychopathology; mother (4q12-q13.1 duplication) ; father (5q32 deletion) had history of speech delay, gradual hearing impairment in past decade, and may have some autistic traits in the social reciprocity domain.
Due to limited communication ability and lack of response to gestyre or verbal commands, case cannot perform intelligence evaluations (such as Weschler Intelligence Scale for Children-3rd ed.) or other neuropsychological tests. Since 1st evaluation, case received early intervention programs (speech therapy & occupational therapy) at 3-5 years, followed by special education programs at kindergarten for 1 year; case is now an 11th grader of high school specialized for mental retardation & autism.
57323576
61868907
4545332
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002576
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
52639018
59984479
7345462
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002652
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
51899860
59984479
8084620
GRCh38
Duplication
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002803
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
54198601
62270115
8071515
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
sanders_11_ASD_discovery_controls-11339.s1
11.2
M
Control (matched sibling)
NA
NA
58569911
58642461
72551
GRCh38
Duplication
No
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
chen_17_ASD_discovery_cases-caseU-2075
RT-qPCR
Maternal
Simplex
RPS26P24,SRIP1,LINC02494,RNU6-1325P,MIR548AG1,RPL17P19,LINC02380,LINC02429,LINC02496,LINC02271,ADGRL3
gau_12_ASD_discovery_cases-case1
qPCR
Maternal
Simplex
RPS26P24,SRIP1,LINC02494,RNU6-1325P,MIR548AG1,RPL17P19,LINC02380,LINC02429,LINC02496,LINC02271,ADGRL3
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002576
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
USP46-AS1,DANCR,MIR4449,SNORA26,RASL11B,RNU6-310P,LNX1-AS2,RPL21P44,MORF4L2P1,RPL22P13,LINC02260,RPL38P3,RNU6-410P,RN7SL424P,RN7SL822P,RNU6-746P,LRRC34P2,FCF1P8,RN7SKP30,RNU6-276P,RNU6-652P,RNA5SP161,RNU6-197P,MRPL22P1,RPL7AP31,GLDCP1,RPL17P20,RN7SL492P,RN7SL357P,RNU6-998P,UBE2CP3,RPS26P24,SRIP1,LINC02494,RNU6-1325P,USP46,ERVMER34-1,LINC01618,FIP1L1,LNX1-AS1,CHIC2,GSX2,LINC02283,KIT,LINC02358,KDR,SRD5A3,SRD5A3-AS1,NMU,EXOC1,PPAT,PAICS,ARL9,THEGL,HOPX,SPINK2,REST,NOA1,IGFBP7,LINC02380,LINC02429,SCFD2,PDGFRA,TMEM165,CLOCK,EXOC1L,CEP135,KIAA1211,AASDH,SRP72,POLR2B,IGFBP7-AS1,LNX1,PDCL2
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002652
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
LINC02480,RNU6-1252P,USP46-AS1,DANCR,MIR4449,SNORA26,RASL11B,RNU6-310P,LNX1-AS2,RPL21P44,MORF4L2P1,RPL22P13,LINC02260,RPL38P3,RNU6-410P,RN7SL424P,RN7SL822P,RNU6-746P,LRRC34P2,FCF1P8,RN7SKP30,RNU6-276P,RNU6-652P,RNA5SP161,RNU6-197P,MRPL22P1,RPL7AP31,GLDCP1,RPL17P20,RN7SL492P,RN7SL357P,RNU6-998P,UBE2CP3,RPS26P24,SRIP1,LINC02494,RNU6-1325P,LRRC66,SPATA18,USP46,ERVMER34-1,LINC01618,FIP1L1,LNX1-AS1,CHIC2,GSX2,LINC02283,KIT,LINC02358,KDR,SRD5A3,SRD5A3-AS1,NMU,EXOC1,PPAT,PAICS,ARL9,THEGL,HOPX,SPINK2,REST,NOA1,IGFBP7,LINC02380,LINC02429,DCUN1D4,SGCB,SCFD2,PDGFRA,TMEM165,CLOCK,EXOC1L,CEP135,KIAA1211,AASDH,SRP72,POLR2B,IGFBP7-AS1,LNX1,PDCL2
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002803
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
De novo
Unknown
Unknown
RPL22P13,LINC02260,RPL38P3,RNU6-410P,RN7SL424P,RN7SL822P,RNU6-746P,LRRC34P2,FCF1P8,RN7SKP30,RNU6-276P,RNU6-652P,RNA5SP161,RNU6-197P,MRPL22P1,RPL7AP31,GLDCP1,RPL17P20,RN7SL492P,RN7SL357P,RNU6-998P,UBE2CP3,RPS26P24,SRIP1,LINC02494,RNU6-1325P,MIR548AG1,RPL17P19,RPS15AP17,RPL21P47,LINC02283,KIT,LINC02358,KDR,SRD5A3,SRD5A3-AS1,NMU,EXOC1,PPAT,PAICS,ARL9,THEGL,HOPX,SPINK2,REST,NOA1,IGFBP7,LINC02380,LINC02429,LINC02496,LINC02271,PDGFRA,TMEM165,CLOCK,EXOC1L,CEP135,KIAA1211,AASDH,SRP72,POLR2B,IGFBP7-AS1,ADGRL3-AS1,PDCL2,ADGRL3
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
sanders_11_ASD_discovery_controls-11339.s1
Paternal
Simplex (quad)
NA
No Animal Model Data Available