15q21.3-q22.2CNV Type: Deletion
Largest CNV size: 8700000 bp
Statistics Box:
Number of Reports: 6
Number of Reports: 6
Summary Information
Summary statement in development
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
Overlapping microdeletions involving 15q22.2 narrow the critical region for intellectual disability to NARG2 and RORA.
Deletion
Minor Reports
Title
Author, Year
Report Class
CNV Type
The clinical utility of molecular karyotyping using high-resolution array-comparative genomic hybridization.
Deletion
Recurrent copy number variations as risk factors for Autism Spectrum Disorders: analysis of the clinical implications.
Deletion
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
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
5451227
2
0
2
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
1200000
0
1
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
5600000
1
0
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
8700000
1
0
1
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)
8700000
1
0
1
yamamoto_14_DD/ID/EP_discovery_cases
Patients with microdeletions involving the 15q22.2 region presenting with neurological symptoms
4
Developmental delay/intellectual disability (all 4 cases), epilepsy (3 cases), and autistic features (1 case)
Range, 3-14 yrs.
50% Male
6500000
3
0
1
Controls
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
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
leppa_16_ASD_discovery_controls
Unaffected children from 1,464 families from the Autism Genetic Resource Exchange (AGRE)
572
Control
N/A
N/A
1200000
0
2
2
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
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
maini_18_ASD/DD/ID_discovery_cases
Italian
aCGH, array SNP
Multiple platforms, including Agilent and Affymetrix arrays (8x60K oligochips since 2012)
None
oikonomakis_16_ASD_discovery_cases
Greece
aCGH
Agilent 244K, 4x180K, or 4x180K (SurePrint G3 arrays)
None
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
yamamoto_14_DD/ID/EP_discovery_cases
N/A
aCGH
Agilent 60K, Agilent 44K
FISH, microarray
Controls
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
kaminsky_11_DD/ID/ASD_discovery_controls
NA
aCGH
Agilent 44K, Agilent 105K
Feature Extraction, DNA Analytics
leppa_16_ASD_discovery_controls
N/A
Solid phase hybridization
Illumina 550v1 and 550v3, Omni-1.0-B and -H, Omni 2.5
PennCNV, QuantiSNP, GNOSIS
GenomeStudio, CNVision
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
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000879
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
57456076
61907285
4451210
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002325
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
57567950
63019415
5451466
GRCh38
Deletion
Yes
leppa_16_ASD_discovery_cases-AU046706
N/A
M
ASD
58571801
59776801
1205001
GRCh38
Duplication
No
maini_18_ASD/DD/ID_discovery_cases-case_unknown41
N/A
N/A
NDD/MCA/dysmorphic features
CNV was identified in an individual with one or more neurodevelopmental disorders (NDD), multiple congenital anomalies (MCA), and/or dysmorphic features (detailed clinical information was not available). CNV classified as pathogenic
55571688
61185835
5614148
GRCh38
Deletion
No
oikonomakis_16_ASD_discovery_cases-case258
3 yrs.
F
ASD
Case was assessed for ASD according to DSM-IV behavioral criteria. Clinical characteristics other than ASD: hypotonia, arched eyebrows, low set ears, microotia, macroglossia, open mouth, drooling
53082409
61810557
8728149
GRCh38
Deletion
No
tzetis_12_DD/ID_discovery_cases-case39
F
DD/ID
Small low set ears with hypoplastic ears, blepharophimosis, macroglossia, arched eyebrows, facial hypotonia with pen mouth appearance
53082409
61810557
8728149
GRCh38
Deletion
No
yamamoto_14_ID/EP_discovery_cases-case1
3 yrs.
F
Developmental delay
Case present in DECIPHER database (DECIPHER ID #271644). Birth/neonatal history: delivered by C-section due to brecch presentation at 37 weeks and 5 days gestation; no complications during pregnancy; birth weight of 2712 g (50th-90th %ile) and OFC of 30.0 cm (<10th %ile). Developmental milestones: motor developmental delay from early infancy; head control at 4 months, rolling over at 12 months, sitting unsupported at 12 months, walking at 31 months; first meaningful word at 11 months of age. Language and communication evaluation: able to understand some simple oral suggestions and speak some meaningful words, but unable to speak more than two words. Behavioral/psychiatric evaluation: self-injurious behavior; often shows startle response when she suddenly hears a loud sound; no sleep disturbance. Brain imaging: cranial tomography showed no abnormalities. Dysmorphic features: frontal bossing, short palpebral fissures, hypertelorism, telecanthus, flat nasal bridge, anteverted nares, thin lips, open mouth, pointed chin, right simian crease, strabismus of left eye. Growth parameters: macrocephaly; height of 80.0 cm (-1.8 SD), weight of 12.3 kg (+0.3 SD), and OFC of 50.8 cm (+2.1 SD).
Mild developmental delay; developmental quotient of 67
55658902
62192217
6533316
GRCh38
Deletion
Yes
yamamoto_14_ID/EP_discovery_cases-case3
13 yrs.
F
Intellectual disability and epilepsy
Case present in DECIPHER database (DECIPHER ID #253216). Birth/neonatal history: born at 41 weeks of gestation; birth weight of 3210 g (50th-75th %ile), length of 50 cm (90th-97th %ile), and OFC of 34.4 cm (75th-90th %ile); unremarkable pregnancy and delivery. Developmental milestones: growth delay at age of 20 months (weight -2.0 SD, height -1.0 SD, OFC -2.0 SD). Language and communication evaluation: no reading or writing skills, poor language skills. Motor and musculoskeletal evaluation: dysmetria, apraxia, ataxia, intention tremor; thin and long fingers, slight clinodactyly of both index fingers. Epilpesy/seizures: experienced spasm associated with syncope and convulsive motion at 20 months of age; status epilepticus at age of 4 years despite prescription of anti-epileptic drugs; intractable complex partial epilepsy. EEG: sleep EEG showed abnormal activities in left hemisphere of brain. Brain imaging: brain MRI showed partial agenesis of the vermis. Dysmorphic features: square face, prominent forehead, short philtrum, up-slanting palpebral fissures, thin lips, pointed chin. Growth parameters: overweight; weight of 42 kg (+1.0 SD), length of 141.5 cm (-2.0 SD), and OFC of 53 cm (mean [M]).
Severe intellectual disability (unable to accurately assess IQ)
57550472
63062011
5511540
GRCh38
Deletion
No
yamamoto_14_ID/EP_discovery_cases-case4
14 yrs.
M
Intellectual disability, epilepsy, and autistic features
Case present in DECIPHER database (DECIPHER ID #270602). Birth/neonatal history: born at 41 weeks of gestation; birth weight of 3400 g (M), length of 52 cm (+2.0 SD), and OFC of 35 cm (M); unremarkable pregnancy. Developmental milestones: head control and following things with his eyes at 4 months; started to walk at age of 24 months; significant delay in language development. Language and communication evaluation: able to speak about 50 meaningful words at age of 11 years. Motor and musculoskeletal evaluation: short hands, pes cavus. Behavioral/psychiatric evaluation: autistic features; no reported sleep disturbances, no abnormal eating behavior. Epilepsy/seizures: patient started to show seizure attacks associated with drooling, which were intractable to antiepileptic treatment, at 3 months of age. Other features: ophthalmological surgery performed to correct strabismus at age of 9 years; puberty has not started in patient. Dysmorphic features: square face, prominent forehead, short philtrum, pointed chin, brachycephaly, downturned corners of mouth, deep-set eyes, prominent ears, strabismus (surgically corrected).
Mild-moderate intellectual disability; estimated developmental quotient of 50
58668900
61223825
2554926
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
leppa_16_ASD_discovery_controls-AU046704
N/A
F
Control
Unaffected sibling
58571801
59776801
1205001
GRCh38
Duplication
No
leppa_16_ASD_discovery_controls-AU046705
N/A
M
Control
Unaffected sibling
58571801
59776801
1205001
GRCh38
Duplication
No
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00000879
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
MTCO3P23,MTND3P12,MTND5P32,MTCYBP23,HMGB1P51,HSP90AB4P,ZNF444P1,MIR2116,LDHAL6B,RNU4-80P,RNU6-212P,RNA5SP396,PIGHP1,MESTP2,CYCSP38,RNA5SP397,LINC02349,POLR2M,AQP9,RN7SKP95,SLTM,GTF2A2,BNIP2,NMNAT1P5,ANXA2,CGNL1,ALDH1A2,LIPC,LIPC-AS1,MINDY2,RNF111,CCNB2,MYO1E,FAM81A,GCNT3,FOXB1,ICE2,RORA-AS1,RORA-AS2,GCOM1,MYZAP,RPS3AP6,RORA,VPS13C,ADAM10
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002325
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Unknown
Unknown
Unknown
MTCO3P23,MTND3P12,MTND5P32,MTCYBP23,HMGB1P51,HSP90AB4P,ZNF444P1,MIR2116,LDHAL6B,RNU4-80P,RNU6-212P,RNA5SP396,PIGHP1,MESTP2,CYCSP38,RNA5SP397,LINC02349,C2CD4A,NPM1P47,C2CD4B,MIR8067,MIR6085,HMGN1P26,MGC15885,MIR190A,POLR2M,AQP9,RN7SKP95,SLTM,GTF2A2,BNIP2,NMNAT1P5,ANXA2,ALDH1A2,LIPC,LIPC-AS1,MINDY2,RNF111,CCNB2,MYO1E,FAM81A,GCNT3,FOXB1,ICE2,RORA-AS1,RORA-AS2,GOLGA2P11,TLN2,GCOM1,MYZAP,RPS3AP6,RORA,VPS13C,ADAM10
leppa_16_ASD_discovery_cases-AU046706
Maternal
Multiplex
Not segregated (CNV not present in affected siblings but is present in unaffected siblings AU046704 and AU046705)
HMGB1P51,HSP90AB4P,ZNF444P1,MIR2116,LDHAL6B,RNU4-80P,RNU6-212P,RNA5SP396,PIGHP1,RN7SKP95,SLTM,GTF2A2,BNIP2,MINDY2,RNF111,CCNB2,MYO1E,FAM81A,GCNT3,RPS3AP6,ADAM10
maini_18_ASD/DD/ID_discovery_cases-case_unknown41
De novo
Unknown
Unknown
CNOT6LP1,RN7SL568P,CD24P2,RNU6-1287P,HMGB1P33,HNRNPA3P11,LINC00926,LINC01413,NDUFB10P1,RNU6-844P,MTCO3P23,MTND3P12,MTND5P32,MTCYBP23,HMGB1P51,HSP90AB4P,ZNF444P1,MIR2116,LDHAL6B,RNU4-80P,RNU6-212P,RNA5SP396,PIGHP1,MESTP2,CYCSP38,RNA5SP397,MNS1,ZNF280D,POLR2M,AQP9,RN7SKP95,SLTM,GTF2A2,BNIP2,NMNAT1P5,ANXA2,PRTG,NEDD4,RFX7,TEX9,TCF12,CGNL1,ALDH1A2,LIPC,LIPC-AS1,MINDY2,RNF111,CCNB2,MYO1E,FAM81A,GCNT3,FOXB1,ICE2,RORA-AS1,RORA-AS2,PYGO1,GCOM1,MYZAP,RPS3AP6,RORA,ADAM10
oikonomakis_16_ASD_discovery_cases-case258
Unknown
RNU2-53P,RNU6-449P,HNRNPA1P74,PIGBOS1,MIR628,CNOT6LP1,RN7SL568P,CD24P2,RNU6-1287P,HMGB1P33,HNRNPA3P11,LINC00926,LINC01413,NDUFB10P1,RNU6-844P,MTCO3P23,MTND3P12,MTND5P32,MTCYBP23,HMGB1P51,HSP90AB4P,ZNF444P1,MIR2116,LDHAL6B,RNU4-80P,RNU6-212P,RNA5SP396,PIGHP1,MESTP2,CYCSP38,RNA5SP397,LINC02349,LINC02490,PIGB,CCPG1,C15orf65,MNS1,ZNF280D,POLR2M,AQP9,RN7SKP95,SLTM,GTF2A2,BNIP2,NMNAT1P5,ANXA2,WDR72,RSL24D1,RAB27A,DNAAF4-CCPG1,DNAAF4,PRTG,NEDD4,RFX7,TEX9,TCF12,CGNL1,ALDH1A2,LIPC,LIPC-AS1,MINDY2,RNF111,CCNB2,MYO1E,FAM81A,GCNT3,FOXB1,ICE2,RORA-AS1,RORA-AS2,UNC13C,PYGO1,GCOM1,MYZAP,RPS3AP6,RORA,ADAM10
tzetis_12_DD/ID_discovery_cases-case39
Unknown
Unknown
RNU2-53P,RNU6-449P,HNRNPA1P74,PIGBOS1,MIR628,CNOT6LP1,RN7SL568P,CD24P2,RNU6-1287P,HMGB1P33,HNRNPA3P11,LINC00926,LINC01413,NDUFB10P1,RNU6-844P,MTCO3P23,MTND3P12,MTND5P32,MTCYBP23,HMGB1P51,HSP90AB4P,ZNF444P1,MIR2116,LDHAL6B,RNU4-80P,RNU6-212P,RNA5SP396,PIGHP1,MESTP2,CYCSP38,RNA5SP397,LINC02349,LINC02490,PIGB,CCPG1,C15orf65,MNS1,ZNF280D,POLR2M,AQP9,RN7SKP95,SLTM,GTF2A2,BNIP2,NMNAT1P5,ANXA2,WDR72,RSL24D1,RAB27A,DNAAF4-CCPG1,DNAAF4,PRTG,NEDD4,RFX7,TEX9,TCF12,CGNL1,ALDH1A2,LIPC,LIPC-AS1,MINDY2,RNF111,CCNB2,MYO1E,FAM81A,GCNT3,FOXB1,ICE2,RORA-AS1,RORA-AS2,UNC13C,PYGO1,GCOM1,MYZAP,RPS3AP6,RORA,ADAM10
yamamoto_14_ID/EP_discovery_cases-case1
FISH
De novo
Likely segregated
CNOT6LP1,RN7SL568P,CD24P2,RNU6-1287P,HMGB1P33,HNRNPA3P11,LINC00926,LINC01413,NDUFB10P1,RNU6-844P,MTCO3P23,MTND3P12,MTND5P32,MTCYBP23,HMGB1P51,HSP90AB4P,ZNF444P1,MIR2116,LDHAL6B,RNU4-80P,RNU6-212P,RNA5SP396,PIGHP1,MESTP2,CYCSP38,RNA5SP397,LINC02349,C2CD4A,NPM1P47,C2CD4B,MNS1,ZNF280D,POLR2M,AQP9,RN7SKP95,SLTM,GTF2A2,BNIP2,NMNAT1P5,ANXA2,PRTG,NEDD4,RFX7,TEX9,TCF12,CGNL1,ALDH1A2,LIPC,LIPC-AS1,MINDY2,RNF111,CCNB2,MYO1E,FAM81A,GCNT3,FOXB1,ICE2,RORA-AS1,RORA-AS2,GCOM1,MYZAP,RPS3AP6,RORA,VPS13C,ADAM10
yamamoto_14_ID/EP_discovery_cases-case3
Unknown
Unknown
MTCO3P23,MTND3P12,MTND5P32,MTCYBP23,HMGB1P51,HSP90AB4P,ZNF444P1,MIR2116,LDHAL6B,RNU4-80P,RNU6-212P,RNA5SP396,PIGHP1,MESTP2,CYCSP38,RNA5SP397,LINC02349,C2CD4A,NPM1P47,C2CD4B,MIR8067,MIR6085,HMGN1P26,MGC15885,MIR190A,TPM1-AS,POLR2M,AQP9,RN7SKP95,SLTM,GTF2A2,BNIP2,NMNAT1P5,ANXA2,CGNL1,ALDH1A2,LIPC,LIPC-AS1,MINDY2,RNF111,CCNB2,MYO1E,FAM81A,GCNT3,FOXB1,ICE2,RORA-AS1,RORA-AS2,GOLGA2P11,TLN2,TPM1,GCOM1,MYZAP,RPS3AP6,RORA,VPS13C,ADAM10
yamamoto_14_ID/EP_discovery_cases-case4
Microarray
De novo
Likely segregated
HMGB1P51,HSP90AB4P,ZNF444P1,MIR2116,LDHAL6B,RNU4-80P,RNU6-212P,RNA5SP396,PIGHP1,MESTP2,CYCSP38,RNA5SP397,RN7SKP95,SLTM,GTF2A2,BNIP2,NMNAT1P5,ANXA2,MINDY2,RNF111,CCNB2,MYO1E,FAM81A,GCNT3,FOXB1,ICE2,RORA-AS1,RORA-AS2,RPS3AP6,RORA,ADAM10
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
leppa_16_ASD_discovery_controls-AU046704
Maternal
Multiplex
HMGB1P51,HSP90AB4P,ZNF444P1,MIR2116,LDHAL6B,RNU4-80P,RNU6-212P,RNA5SP396,PIGHP1,RN7SKP95,SLTM,GTF2A2,BNIP2,MINDY2,RNF111,CCNB2,MYO1E,FAM81A,GCNT3,RPS3AP6,ADAM10
leppa_16_ASD_discovery_controls-AU046705
Maternal
Multiplex
HMGB1P51,HSP90AB4P,ZNF444P1,MIR2116,LDHAL6B,RNU4-80P,RNU6-212P,RNA5SP396,PIGHP1,RN7SKP95,SLTM,GTF2A2,BNIP2,MINDY2,RNF111,CCNB2,MYO1E,FAM81A,GCNT3,RPS3AP6,ADAM10
No Animal Model Data Available