2q22.3-q23.1CNV Type: Deletion
Largest CNV size: 2400000 bp
Statistics Box:
Number of Reports: 7
Number of Reports: 7
Summary Information
A de novo deletion in this region containing the MBD5 gene was identified in a case diagnosed with mental retardation, autistic behavior and epilepsy.
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
2q23.1 microdeletion identified by array comparative genomic hybridisation: an emerging phenotype with Angelman-like features?
Deletion
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabili...
Deletion
A cryptic microdeletion including MBD5 occurring within the breakpoint of a reciprocal translocation between chromosomes 2 and 5 in a patient with ...
Deletion
Disruption of MBD5 contributes to a spectrum of psychopathology and neurodevelopmental abnormalities.
Deletion
Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy.
Deletion
Minor Reports
Title
Author, Year
Report Class
CNV Type
Reciprocal deletion and duplication at 2q23.1 indicates a role for MBD5 in autism spectrum disorder.
Duplication
Rare Inherited and De Novo CNVs Reveal Complex Contributions to ASD Risk in Multiplex Families.
Duplication
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
fry_16_DD/ID/EP/ASD_discovery_cases
Participants recruited between 2010 and 2014 and identified through medical genetics, learning disability, and pediatric neurology clinics around Wales
80
All cases presented with childhood-onset epilepsy (25 with epileptic encephalopathy, 22 with non-lesional focal epilepsies, 22 with genetic generalized epilepsy with ID, 11 unclassified or unknown) and developmental delay (DD) or intellectual disability (ID)
Range, <1 yr.-60 yrs.
45.0% Male
127000
1
0
1
hodge_13_DD/ID/ASD_discovery_cases
Previously unpublished patients with 2q23.1/MBD5 microdeletions from the Mayo Clinic Cytogenetics Laboratory (cases 1-8), the Greenwood Genetic Center (cases 9-12), Pathology Associates Medical Laboratories (cases 13-14), Virginia Commonwealth University (case 15), Fullerton Genetics Center (case 16), and Boston Children's Hospital (case 17)
17
Phenotypes typically associated with 2q23.1 microdeletion syndrome (developmental delay/intellectual disability (DD/ID), ASD or autistic features, etc.). Two cases with bipolar disorder, one case with behavioral regression.
Range, <1 yr.-44 yrs.
52.94% Male
1256080
5
0
5
jaillard_09_DD_discovery_cases
Cases recruited at clinical genetic dept. of Rennes University Hospital and Robert Debr University Hospital, Paris
2
Both cases with severe psychomotor retardation, severe language impairment, epilepsy, ataxia, microcephaly, and beahvioral disabilities. One case with autistic features.
10 yrs
Male
2400000
1
0
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
1256080
3
0
3
leppa_16_ASD_discovery_cases
Children affected with ASD from 1,464 families from the Autism Genetic Resource Exchange (AGRE)
1764
Diagnosis according to ADOS and ADI-R
N/A
N/A
500000
0
1
1
mullegama_13_ASD/DD/ID_discovery_cases
Individuals with 2q23.1/MBD5 duplications; two cases previously reported in Chung et al. Eur J Hum Genet 2012 report. Only individuals with defined duplication start and end points (from Supplemental Table 1)were annotated.
30
Most prevalent phenotypic features: developmental delay (DD), motor delay, language impairment, behavioral problems, ASD/autistic features.
N/A
N/A
9986000
0
5
5
shichiji_13_DD/EP_discovery_cases
3-year-old girl born to healthy nonconsanguineous parents with de novo reciprocal translocation between chromosomes 2 and 5 [t(2;5)(q23;q22)].
1
Developmental delay, epilepsy, autistic behaviors (stereotypies), and obesity
3 yrs.
Female
896000
1
0
1
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
36570
0
1
1
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
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
fry_16_DD/ID/EP/ASD_discovery_cases
78 White British, 1 South Asian, 1 Mixed White/South Asian
aCGH, solid phase hybridization
Illumina610-Quad SNP-array, Illumina OmniExpress SNP-array, BlueGnome CytoChip ISCA 8x60k v2.0 array
PennCNV
Illumina BlueFuse Multi v3.1
Solid phase hybridization (Illumina)
hodge_13_DD/ID/ASD_discovery_cases
N/A
aCGH, array SNP
Agilent 180K, Agilent 44K, Agilent 105K, Oxford Gene Technology Plus 105K, Affymetrix 6.0, Affymetrix Cytoscan HD
FISH, qPCR, array SNP (Affymetrix Cytoscan HD Array )
jaillard_09_DD_discovery_cases
French
aCGH
Agilent 4x44K, BACs aCGH
GenePix Pro 6, GenoCensus
FISH, PCR
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
leppa_16_ASD_discovery_cases
N/A
Solid phase hybridization
Illumina 550v1 and 550v3, Omni-1.0-B and -H, Omni 2.5
PennCNV, QuantiSNP, GNOSIS
GenomeStudio, CNVision
None
mullegama_13_ASD/DD/ID_discovery_cases
N/A
N/A
N/A
N/A
shichiji_13_DD/EP_discovery_cases
Japanese
aCGH
Agilent Human Genomic CGH Microarray 44A
FISH
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
Cases
Patient ID
Author, Year
Age
Gender
Primary Diagnosis
Clinical Profile
Cognitive Profile
CNV Start
CNV End
CNV Size
Genome Build
Type Method
Validation
fry_16_DD/ID/EP/ASD_discovery_cases-caseR911
22 yrs.
F
Intellectual disability and epilepsy
Clinical features: moderate intellectual disability, small head, mild dysmorphic features (long face, thin upper lip, slightly upslanting palpebral fissures, long nose). Age of seizure onset: 10 years. Epilepsy syndrome: focal epilepsy. Seizure types: focal dyscognitive seizures, generalized tonic-clonic seizures.
Moderate intellectual disability
147934304
148060868
126565
GRCh38
Deletion
Yes
hodge_13_DD/ID/ASD_discovery_cases-case1
19 yrs.
F
DD/ID/ASD
New phenotypic features: none.
147251948
148349192
1097245
GRCh38
Deletion
Yes
hodge_13_DD/ID/ASD_discovery_cases-case15
7 yrs.
M
DD/ID/ASD
New phenotypic features: none.
147911593
148022711
111119
GRCh38
Deletion
Yes
hodge_13_DD/ID/ASD_discovery_cases-case17
6 yrs.
M
DD/ID/ASD
New phenotypic features: none.
147746214
148658191
911978
GRCh38
Deletion
Yes
hodge_13_DD/ID/ASD_discovery_cases-case2
2 yrs.
M
DD/ID/ASD
New phenotypic features: none.
147680433
148220153
539721
GRCh38
Deletion
Yes
hodge_13_DD/ID/ASD_discovery_cases-case3
44 yrs.
M
DD/ID/ASD
New phenotypic features: cataracts, behavioral regression (worsening skin picking and obsessive-compulsive actions), anxiety, bipolar disorder
147783116
148948475
1165360
GRCh38
Deletion
Yes
jaillard_09_DD_discovery_cases-subject2
10 yrs.
M
Developmental delay
Case referred to genetics clinic for mental retardation, autistic behavior, ataxia, and epilepsy. Birth/neonatal history: unremarkable pregnancy and birth at 39 weeks; macrosomic neonatal measurements (weight >97th %ile, height 95th %ile, head circumference 90th %ile); neonatal feeding difficulties (swallowing troubles and gastro-esophageal reflux); too calm and did not cry. Langauge and communication evaluation: severe language impairment; emitted some dissyllabic sounds, did not express any significant words. Motor and musculoskeletal evaluation: severe psychomotor retardation was progressively discovered (retarded sitting position); unaided walking at 34 months with ataxia; poor balance; brisk reflexes. Behavioral/psychiatric evaluation: frequent smiles, unmotivated bursts of laughter, autistic behavior (eye avoidance, hand flapping, bruxism, elevated anxiety in new surroundings); tendency of stereotypies present on median line, which was amplified by stress; auto and hetero-aggression noted, with self-biting of hands and forearms; decreased pain sensitivity (no reaction to bites and injuries). Sleep disturbances: perturbed sleep patterns with multiple awakenings in the night. Epilepsy/seizures: epilepsy began at 3 years , treated by valproate. EEG: normal. Brain imaging: brain MRI showed large pericerebral spaces and relative macrocephaly with hypoplasia of frontal lobes. Vision: normal visual evoked potentials. Hearing: normal auditory evoked potentials. Dysmorphic features: brachycephaly, low implantation of hair on neck, pronounced midface hypoplasia, short columella, large mouth, prognathism, macroglossia, small spaced teeth, secondarily hypodeveloped genitalia, shirt hands with thick striated skin, bilateral 5th clinodactyly. Other medical concerns and comorbidities: frequent dribbling, poorly mineralized skeleton and brachymesophalangy on Xrays. Growth parameters: height and head circumference at median; weight -1 SD. Family history: only child of young non-consanguineous parents of French origin.
Mental retardation
146891000
149268000
2400000
Unknown
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000806
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
147713771
148177277
463507
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00003836
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
147783116
148948475
1165360
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004510
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
147251948
148349192
1097245
GRCh38
Deletion
Yes
leppa_16_ASD_discovery_cases-AU3912302
N/A
M
ASD
147519432
148024431
505000
GRCh38
Duplication
No
mullegama_13_ASD/DD/ID_discovery_cases-caseChung_2_2012
17 yrs.
F
DD and ASD/autistic features
Neurological/behavioral evaluation: developmental delay, motor delay, language impairment, autistic-like features, likeable/affable personality, behavioral problems, infantile hypotonia. Dysmorphic features: craniofacial abnormalities, arched eyebrows, bilateral ptosis, long eyelashes, hypotelorism, prominent nose, wide mouth, unspecificed dental abnormalities, hand/foot abnormalities, 5th finger clinodactyly, large broad first toe. Ocular evaluation: strabismus, visual impairment.
Developmental delay
147712171
149623732
1911562
GRCh38
Duplication
No
mullegama_13_ASD/DD/ID_discovery_cases-caseGC22689
N/A
N/A
DD and ASD/autistic features
N/A
N/A
147742868
148114605
371738
GRCh38
Duplication
No
mullegama_13_ASD/DD/ID_discovery_cases-caseGC60276
N/A
N/A
DD and ASD/autistic features
N/A
N/A
144796723
153488227
8691505
GRCh38
Duplication
No
mullegama_13_ASD/DD/ID_discovery_cases-caseMayo1
12 yrs.
F
DD and ASD/autistic features
Neurological/behavioral evaluation: developmental delay, motor delay, language impairment, autistic-like features, behavioral problems, infantile hypotonia. Dysmorphic features: craniofacial anomalies.
Developmental delay
146324191
156219125
9894935
GRCh38
Duplication
No
mullegama_13_ASD/DD/ID_discovery_cases-caseSMS381
6 yrs.
M
DD and ASD/autistic features
Neurological/behavioral evaluation: developmental delay, motor delay, language impairment, autistic-like features, likeable/affable personality, behavioral problems, seizures, infantile hypotonia. Dysmorphic features: craniofacial anomalies, pinnae abnormalities, hand/foot abnormalities.
Developmental delay
147925961
149035240
1109280
GRCh38
Duplication
No
shichiji_13_DD/EP_discovery_cases-case1
3 yrs.
F
Developmental delay and epilepsy
Birth/neonatal history: born at gestational age of 40 weeks 5 days without complications; birth weight +3.1 SD, length +1.7 SD, OFC +1.5 SD. Developmental milestones: mild psychomotor developmental delay (based on inability to stand without assistance and to speak any meaningful words aside from babbling) noted at 12 months; started to walk at 17 months and eat using a fork at 22 months. Langauge and communication evaluation: unable to speak any meaningful words at age of 2 years. Motor and musculoskeletal evaluation: ataxic gait. Behavioral/psychiatric evaluation: stereotypic movements of the mouth; hyperphagia (cause of patient's obesity). Epilepsy/seizures: first epileptic attack at age of 2 years (triggered by fever), followed by subsequent clustering of epileptic attacks without high fever; seizure attacks well controlled by treatment with anti-epileptic drugs. EEG: spike at slow-wave complexes and multiple delta waves on left occipital lobe at age of 2 years. Brain imaging: brain MRI performed at age of 3 years showed mildly reduced cerebral volume and pachygyria in left occipital lobe. Dysmorphic features: fair skin, brachycephaly, arched eyebrows, prominent lip, drooping mouth corner; short 5th fingers; short 4th and 5th toes; bilateral defects of 12th ribs. Growth parameters: obesity (BMI of 20.1; >97th %ile); height of 93.3 cm (+0.2 SD), weight of 17.5 kg (+3 SD), and OFC of 47.5 cm (-0.5 SD) at age of 2 years 9 months. Family history: first child born to healthy nonconsanguineous parents. Karyotype: de novo translocation between chromosomes 2 and 5; 46,XX,t(2;5)(q23;q22).
Moderate developmental delay; developmental quotient based on Kyoto Scale of Psychological Development Test was 38
147874690
148771274
896585
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-controlB974346_1007875852
N/A
N/A
Control
No previous psychiatric history
147922691
147959261
36571
GRCh38
Duplication
No
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
fry_16_DD/ID/EP/ASD_discovery_cases-caseR911
Solid phase hybridization (Illumina)
De novo
ORC4,MBD5
hodge_13_DD/ID/ASD_discovery_cases-case1
FISH
De novo
Unknown
Unknown
RNU6-692P,RNU6-715P,RNA5SP106,RNU6-1275P,ORC4,MBD5,ACVR2A
hodge_13_DD/ID/ASD_discovery_cases-case15
FISH
Unknown
Unknown
Unknown
ORC4,MBD5,ACVR2A
hodge_13_DD/ID/ASD_discovery_cases-case17
qPCR
De novo
Unknown
Unknown
RNU6-1275P,RPS29P8,ORC4,MBD5,EPC2,ACVR2A
hodge_13_DD/ID/ASD_discovery_cases-case2
FISH
Unknown
Unknown
Unknown
RNA5SP106,RNU6-1275P,ORC4,MBD5,ACVR2A
hodge_13_DD/ID/ASD_discovery_cases-case3
FISH
De novo
Unknown
Unknown
RNU6-1275P,RPS29P8,RNU2-9P,UBBP3,ORC4,MBD5,EPC2,ACVR2A,KIF5C
jaillard_09_DD_discovery_cases-subject2
FISH
De novo
Simplex
Likely segregated
ACVR2A, ORC4L, MBD5, EPC2
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000806
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
RNU6-1275P,ORC4,MBD5,ACVR2A
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00003836
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
RNU6-1275P,RPS29P8,RNU2-9P,UBBP3,ORC4,MBD5,EPC2,ACVR2A,KIF5C
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00004510
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
RNU6-692P,RNU6-715P,RNA5SP106,RNU6-1275P,ORC4,MBD5,ACVR2A
leppa_16_ASD_discovery_cases-AU3912302
Paternal
Multiplex
Not segregated (CNV not present in affected sibling)
RNA5SP106,RNU6-1275P,ORC4,MBD5,ACVR2A
mullegama_13_ASD/DD/ID_discovery_cases-caseChung_2_2012
Unknown
Unknown
Unknown
RNA5SP106,RNU6-1275P,RPS29P8,RNU2-9P,UBBP3,TXNP5,FAM8A3P,RNU6-601P,MMADHC,ORC4,MBD5,EPC2,LYPD6B,LYPD6,ACVR2A,KIF5C
mullegama_13_ASD/DD/ID_discovery_cases-caseGC22689
Unknown
Unknown
Unknown
RNU6-1275P,ORC4,MBD5,ACVR2A
mullegama_13_ASD/DD/ID_discovery_cases-caseGC60276
Unknown
Unknown
Unknown
LINC01966,RPL6P5,RNU7-2P,RNU6-692P,RNU6-715P,RNA5SP106,RNU6-1275P,RPS29P8,RNU2-9P,UBBP3,TXNP5,FAM8A3P,RNU6-601P,FABP5P10,MIR4773-2,MIR4773-1,RN7SL124P,RPL30P2,UBQLN4P2,ATP5PBP4,RPRM,RPL17P12,PABPC1P2,LINC01911,MMADHC,LINC01817,LINC01920,NMI,TNFAIP6,RIF1,ARL5A,ARL6IP6,RPL23AP29,ORC4,MBD5,EPC2,LYPD6B,LYPD6,LINC01931,LINC01818,RND3,RBM43,NEB,STAM2,FMNL2,PRPF40A,LINC01850,TEX41,ACVR2A,KIF5C,CACNB4
mullegama_13_ASD/DD/ID_discovery_cases-caseMayo1
Unknown
Unknown
Unknown
RNU6-692P,RNU6-715P,RNA5SP106,RNU6-1275P,RPS29P8,RNU2-9P,UBBP3,TXNP5,FAM8A3P,RNU6-601P,FABP5P10,MIR4773-2,MIR4773-1,RN7SL124P,RPL30P2,UBQLN4P2,ATP5PBP4,RPRM,DNAJA1P2,PHBP4,RNA5SP107,CBX3P6,RNU6-1001P,MTCO1P45,MTND2P20,ATP5F1AP2,MTND4P28,MTND5P30,MTND6P9,MTCYBP9,RNU6-546P,PABPC1P2,LINC01911,MMADHC,LINC01817,LINC01920,NMI,TNFAIP6,RIF1,ARL5A,ARL6IP6,RPL23AP29,ORC4,MBD5,EPC2,LYPD6B,LYPD6,LINC01931,LINC01818,RND3,RBM43,NEB,STAM2,FMNL2,PRPF40A,LINC01850,KCNJ3,ACVR2A,KIF5C,CACNB4,GALNT13,LINC01876
mullegama_13_ASD/DD/ID_discovery_cases-caseSMS381
Unknown
Unknown
Unknown
RPS29P8,RNU2-9P,UBBP3,ORC4,MBD5,EPC2,ACVR2A,KIF5C
Increased MBD5 expression (as determined by qPCR in patient LCLs)
shichiji_13_DD/EP_discovery_cases-case1
FISH
De novo
RNU6-1275P,RPS29P8,ORC4,MBD5,EPC2,ACVR2A
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
engchuan_15_ASD_discovery_controls-controlB974346_1007875852
Unknown
ORC4,ACVR2A
No Animal Model Data Available