22q11.2CNV Type: Duplication
Largest CNV size: 3000000 bp
Statistics Box:
Number of Reports: 7
Number of Reports: 7
Summary Information
Duplications within the DiGeorge Syndrome region (22q11.21) were identified.
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
Multiplex ligation-dependent probe amplification for genetic screening in autism spectrum disorders: efficient identification of known microduplica...
Duplication
Array comparative genomic hybridization findings in a cohort referred for an autism evaluation.
Duplication
22q11 deletion syndrome and multiple complex developmental disorder: a case report.
Deletion
Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder.
Deletion
Minor Reports
Title
Author, Year
Report Class
CNV Type
Microduplication 22q11.2 in a child with autism spectrum disorder: clinical and genetic study.
Duplication
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
cai_08_ASD_discovery_cases
Unrelated individuals with autism or ASD recruited by SARC and/or AGRE
279
270 cases diagnosed with autism, 2 with Asperger's, 1 with PDD-NOS, 3 with not quite autism (NQA), 3 with broad spectrum autism
Mean 7.94 yrs
79.6% Male
3000000
0
2
2
chen_11_ASD_discovery_cases
Unrelated ASD cases from multiplex families ( 2 children with ASD); many of these families have been previously used in genetics studies (2 linkage studies, 1 rare single gene mutation study).
513
Diagnosis of autism or ASD based on meeting DSM-IV criteria following assessment by trained clinicians using ADI-R & ADOS-G
3000000
0
2
2
mukaddes_07_ASD_discovery_cases
9-year-old female with ASD
1
ASD
9
Female
N/A
0
1
1
munnich_19_ASD_discovery_cases
Children and young adults with ASD recruited from 26 day-care hospitals and specialized institutions within the Greater Paris region
502
Diagnosis of ASD based on DSM criteria, with standardized clinical assessment performed using CARS, ADOS, and/or ADI-R
< 10 years, 34 cases; 11-20 years, 194 cases; 21-30 years, 211 cases; > 30 years, 63 cases
69.92% Male
N/A
1
0
1
ramelli_08_ASD_discovery_cases
4-year-old male diagnosed with ASD
1
ASD
4
Male
N/A
0
1
1
scandurra_13_ASD_discovery_cases
Caucasian male patient born to healthy unrelated patients with 22q11.2 deletion
1
ASD and psychotic disorders (anxiety disorder, separation anxiety disorder, ADHD-like features). Diagnosis of ASD based on ADOS module 4 and ADI-R evaluation. Other diagnostic tools used in assessing case include WISC-III, VABS-II, CBCL/4-18, CPRS-R:L, and K-SADA-PL.
15 yrs.
Male
1500000
1
0
1
schaefer_10_ASD_discovery_cases
Patients selected for aCGH studies between 2005 and 2007 at Human Genetics Laboratory at Univ. of Nebraska
68
Primary indication noted on request form of autism. 54 patients with simple (non-syndromic) autism, 14 patients with complex (syndromic) autism.
NA
0
2
2
Controls
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
cai_08_ASD_discovery_cases
205 Caucasian, 6 African-American, 24 Hispanic or Latino, 5 Asian, 11 mixed ethnicity, 28 unknown
MLPA
ABI 3130 genetic analyzer (Applied Biosystem)
GeneMarker
Direct DNA sequencing qPCR, FISH
chen_11_ASD_discovery_cases
80% White, 10% mixed-race, 10% US minorities
qPCR
Taqman copy number assay/Applied Biosystems 7500 Real-Time PCR system
Copy Caller Software V1.0 (Applied Biosystems)
aCGH (custom Agilent 400K oligo array)
mukaddes_07_ASD_discovery_cases
Middle Eastern
FISH
munnich_19_ASD_discovery_cases
France
aCGH, karyotyping
Agilent 60K
FISH
ramelli_08_ASD_discovery_cases
European
FISH
scandurra_13_ASD_discovery_cases
Caucasian
aCGH
N/A
MLPA
schaefer_10_ASD_discovery_cases
aCGH
Spectral Genomics Constitutional Array, Spectral Chip 2600 Array (1 Mb)
GenePix Pro 6.0, SpectralWare CGH analysis software
FISH
Controls
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
cai_08_ASD_discovery_controls
Caucasian
qPCR
ABI Prism 7900 HT (Applied Biosystem)
Sequence Detection
Cases
Patient ID
Author, Year
Age
Gender
Primary Diagnosis
Clinical Profile
Cognitive Profile
CNV Start
CNV End
CNV Size
Genome Build
Type Method
Validation
cai_08_ASD_discovery_cases-AU001804
4.1
M
Autism
Non-verbal language 10, Repetitive behavior 6, Onset 5, Raven 131, epicanthal folds, prominent ears, retrognathia, ligamentous laxity
NA
3000000
Unknown
Duplication
Yes
cai_08_ASD_discovery_cases-AU004903
5.7
F
Autism
Non-verbal language 13, Repetitive behavior 6, Onset 4, Raven 83, epicanthal folds, midface hypoplasia, abnormal pigmentation
NA
3000000
Unknown
Duplication
Yes
chen_11_ASD_discovery_cases-caseAU142-03
F
Autism
Family history: monozygotic twin sister has paternally-inherited 22q11.2 duplication & diagnosis of ASD; father showed decreased social motivation and limited range of interests/flexibility as assessed by Broader Phenotype Autism Symptom Scale (BPASS).
Low IQ (full-scale IQ 49)
17000000 (approximate)
20000000 (approximate)
3000000
Unknown
Duplication
Yes
chen_11_ASD_discovery_cases-caseM2017-03
M
Autism
Family history: sister, who has diagnosis of autism/ASD, lacks 22q11.2 duplication
17000000 (approximate)
20000000 (approximate)
3000000
Unknown
Duplication
Yes
davis_09_ASD_discovery_cases-AU1437302
NA
NA
Syndromic ASD
Diagnosis: autism. Syndromic autism features: cleft lip and palate
21031117
21651381
230304
Unknown
Deletion
No
mukaddes_07_ASD_discovery_cases-patient1
9
F
ASD
Impaired social skills, stereotypical behaviors, delayed motor and speech, facial dysmorphism
NA
N/A
Unknown
Duplication
No
munnich_19_ASD_discovery_cases-case17
N/A
M
ASD
Case diagnosed with ASD based on DSM criteria. CNV detected by karyotype and FISH analysis (probes RP11-316L10 and RP11-1107K6, location 22q11.2, locusTBX1).
N/A
N/A
N/A
GRCh37
Deletion
Yes
ramelli_08_ASD_discovery_cases-patient1
4
M
ASD
Developmental delay, no verbal communication skills, repetitive behaviors, severe lack of social interactions
NA
N/A
Unknown
Duplication
No
scandurra_13_ASD_discovery_cases-case1
15 yrs.
M
ASD and psychotic disorders
Assessment results using ADOS-module 4: communication score of 4 (> cut-off autism); social interaction score of 5 (>ASD); total (communication and social interaction) score of 9 (>ASD); imagination score of 1; stereotyped behavior and restricted interests score of 2. Assessment results using ADI-R: reciprocal social interaction score of 14 (>ASD); communication score of 13 (>ASD); restricted, repetitive, and stereotyped patterns of behaviors score of 10 (>ASD); abnormality of development evident at or before 36 months score of 3 (>ASD). K-SADS-PL assessment: anxiety disorders; Separation Anxiety Disorder (SAD). CBCL/4-18 assessment: withdrawn score of 88-C (>98th %ile); somatic complaints score of 91-C (>98th %ile); anxious/depressed score of 81-C (>98th %ile); social problems score of 87-C (>98th %ile); thought problems score of 82-C (>98th %ile); attention problems score of 89C (>98th %ile); aggressive behavior score of 68-B (97th %ile). CPRS-R:L assessment: oppositional score of 78; cognitive/inattentive score of 69; hyperactivity score of 76; anxious/shy score of 97; perfectionism score of 62; social problems score of 100; psychosomatic score of 99; Conners' ADHD Index score of 79; I:CGI Restlessness-Impulsive score of 71; J-CGI-Emotional Lability score of 83; K-CGI Total score of 76; L:DSM-IV Inattentive score of 76; M-DSM-IV Hyperactive-Impulsive score of 76; DSM-IV total score of 79. Developmental milestones: slightly delayed psychomotor development (sitting at 11 months, walking at 18 months); first words at 12 months, complete phrases at 24 months; pointing at objects present at 30 months (other communicative gestures were poor); developed literal comprehension of language with difficulties understanding metaphorical sentences. Motor and musculoskeletal evaluation: mildly reduced muscle tone, reported fatigue, normal muscle trophism; patient able to walk and run; global clumsiness; poor fine motor skills; hyperlaxity of ligaments, flat feet. Behavioral/psychiatric evaluation: extensive neuropsychiatric evaluation (see above); poor interaction with peers, difficulties in modulating social interaction with peers (excessive intrusiveness or avoidance); development of selective interest in limited range of objects; excessive anxiety concerning separation from parents; occassional aggressive behavior toward family members; ADHD-like features of hyperactivity, impulsivity, and inattention. EEG: normal. Brain imaging: brain MRI within normal limits. Ohter features: immunological profile showed mild IgG-IgM reduction, mild lynphopenia, and hypo-gamma-globulinemia. Dysmorphic features: mild facial dysmorphisms (long face, ocular hypertelorism, small ears, prominent nose with bulbous tip). Family history: born to healthy unrelated parents; healthy younger sister.
WISC-III assessment results: full scale IQ of 77, verbal IQ of 90, performance IQ of 69; verbal comprehension score of 93; perceptual organization score of 72; freedom from distractibility score of 78; processing speed score of 85. VABS-II assessment results: adaptive behavior composite score of 61 (communication score of 59, daily living skills score of 63, socialization score of 64, motor skills score of 75, maladaptive behavior scale index was clinically significant)
N/A
N/A
1500000
Unknown
Deletion
Yes
schaefer_10_ASD_discovery_cases-case1
NA
M
Autism
Simple (non-syndromic autism). Behavior problems. No dysmorphisms.
Developmental delay
NA
NA
NA
Unknown
Duplication
Yes
schaefer_10_ASD_discovery_cases-case10
NA
F
Autism
Complex (syndromic) autism. Hypotonia. Microcephaly, macrostomia, esotropia.
Developmental delay
NA
NA
NA
Unknown
Duplication
Yes
Controls
No Control Data Available
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
cai_08_ASD_discovery_cases-AU001804
FISH
Paternal
Multiplex
Not segregated
cai_08_ASD_discovery_cases-AU004903
FISH
De novo
Multiplex
Not segregated
chen_11_ASD_discovery_cases-caseAU142-03
aCGH (custom Agilent 400K oligo array)
Possibly paternal
Paternal
Multiplex
Segregated
Approximate gene content: USP18,DGCR6,PRODH,DGCR2,DGCR14,TSSK2,GSC2,SLC25A1,CLTCL1,HIRA,MRPL40,C22orf39,UFD1L,CDC45,CLDN5,SEPT5,GP1BB,TBX1,GNB1L,C22orf29,TXNRD2,COMT,ARVCF,C22orf25,DGCR8,TRMT2A,RANBP1,ZDHHC8,LOC388849,RTN4R,DGCR6L,TMEM191B,RIMBP3,ZNF74,SCARF2,KLHL22,MED15,PI4KA,SERPIND1,SNAP29,CRKL,AIFM3,LZTR1,THAP7,P2RX6,SLC7A4
chen_11_ASD_discovery_cases-caseM2017-03
aCGH (custom Agilent 400K oligo array)
De novo
Multiplex
Approximate gene content: USP18,DGCR6,PRODH,DGCR2,DGCR14,TSSK2,GSC2,SLC25A1,CLTCL1,HIRA,MRPL40,C22orf39,UFD1L,CDC45,CLDN5,SEPT5,GP1BB,TBX1,GNB1L,C22orf29,TXNRD2,COMT,ARVCF,C22orf25,DGCR8,TRMT2A,RANBP1,ZDHHC8,LOC388849,RTN4R,DGCR6L,TMEM191B,RIMBP3,ZNF74,SCARF2,KLHL22,MED15,PI4KA,SERPIND1,SNAP29,CRKL,AIFM3,LZTR1,THAP7,P2RX6,SLC7A4
davis_09_ASD_discovery_cases-AU1437302
Unknown
Unknown
Unknown
ZNF280B, ZNF280A, PRAME, GGTLC2
mukaddes_07_ASD_discovery_cases-patient1
Paternal
Simplex
NA
munnich_19_ASD_discovery_cases-case17
FISH
Unknown
CNV gene content N/A
ramelli_08_ASD_discovery_cases-patient1
De novo
Simplex
NA
scandurra_13_ASD_discovery_cases-case1
MLPA
Unknown
Simplex
Unknown
N/A
schaefer_10_ASD_discovery_cases-case1
FISH
Unknown
Unknown
Unknown
NA
schaefer_10_ASD_discovery_cases-case10
FISH
Unknown
Unknown
Unknown
NA
Controls
No Control Data Available
h22q11.2->m16qA3
# of Model: 5
# of References: 7
# of References: 7
Mouse Chromosome Information
This mouse model features a deletion in the qA3 locus of chromosome 16, ranging from Dgcr2 to Hira. It is syntenic to a 1.5-Mb microdeletion in the q11.21 locus of human chromosome 22.
Model Summary
This is a mouse model of a 22q11.21 microdeletion that has been observed in individuals with autism and other neuropsychiatric disorders. Mice with this microdeletion display sensory, learning, and memory deficits.
External Links
References
Report Type
Title
Author, Year
Additional
Mice deleted for the DiGeorge/velocardiofacial syndrome region show abnormal sensorimotor gating and learning and memory impairments.
Additional
Behavior of mice with mutations in the conserved region deleted in velocardiofacial/DiGeorge syndrome.
Primary
Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model.
Additional
Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome.
Additional
Neuroanatomical phenotypes in a mouse model of the 22q11.2 microdeletion.
Additional
The pattern of cortical dysfunction in a mouse model of a schizophrenia-related microdeletion.
Additional
Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental deficits in a 22q11 deletion syndrome mouse model.