14q24.3-q31.1CNV Type: Deletion
Largest CNV size: 74550 bp
Statistics Box:
Number of Reports: 7
Number of Reports: 7
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
Evaluation of copy number variations reveals novel candidate genes in autism spectrum disorder-associated pathways.
Deletion
Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature.
Deletion
The clinical significance of small copy number variants in neurodevelopmental disorders.
Deletion
Minor Reports
Title
Author, Year
Report Class
CNV Type
Rare structural variation of synapse and neurotransmission genes in autism.
Deletion
Paternally inherited cis-regulatory structural variants are associated with autism.
Deletion
A rare exonic NRXN3 deletion segregating with neurodevelopmental and neuropsychiatric conditions in a three-generation Chinese family.
Deletion
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
asadollahi_14_NDD_discovery_cases
Patients screened for rare non-polymorphic exonic CNVs sizing 1-500 kb
714
Patients with undiagnosed neurodevelopmental disorders (NDD) with or without further congenital anomalies
N/A
N/A
462000
1
0
1
bena_13_ASD/DD/ID_discovery_cases
Previously unreported individuals with NRXN1 exonic deletions recruited as part of a multicenter study
25
Diagnosis of ASD in 65% of cases (diagnostic tools N/A). Other recurrent diagnoses: intellectual disability (91%), language delay (81%), seizures (43%), and hypotonia (38%).
Range, 5-59 yrs.
76.0% Male
300000
1
0
1
brandler_18_ASD_replication_cases
Affected individuals from MSSNG cohort (1395 cases from 1187 families) and the Simons Simplex 2 (SSC2) cohort (584 cases from simplex quad families)
1979
Cases diagnosed with ASD
N/A
N/A
289429
6
0
6
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
74550
1
0
1
griswold_12_ASD_discovery_cases
Unrelated ASD cases from the Collaborative Autism Project (CAP) ascertained through clinical groups at the University of Miami (HIHG), the University of South Carolina, and Vanderbilt University. 260 cases from multiplex families, 483 from simplex families, 62 from families with siblings having autistic-like traits without a confirmed ASD diagnosis, and 8 from families with monozygotic twins.
813
Daignosis of ASD/autism. Inclusion criteria: (1) age between 3-21 years, (2) presumptive clinical diagnosis of autism, (3) expert clinical determination of autism diagnosis using DSM-IV criteria supported by ADI-R in the majority of cases and all available clinical information, (4) minimal developmental level of 18 months as determined by VABS or VABS-II or IQ equivalent >35. Exclusion criteria: severe sensory problems, significant motor impairments, or previously identified metabolic, genetic, or progressive neurological disorder.
Range, 3-21 yrs.
NA
132718
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
4121280
1
0
1
yuan_18_ASD/ADHD/ID_discovery_cases
7-year-old male proband from a three-generation Chinese family in which a 222 kb heterozygous 14q24.3-q31.3 microdeletion affecting the NRXN3 gene segregated with neurodevelopmental and neuropsychiatric phenotypes
1
Case was initially diagnosed with ASD after clinical assessment at 2 years 5 months; reassessment at 3 years 8 months confirmed that he met the clinical diagnostic criteria for autism based on ABC, CARS, and Modified Checklist for Autism in Toddlers Revised. The case also presented with ADHD and moderate intellectual disability (as determined by the Wechsler Intelligence Scale).
7 years
Male
222000
1
0
1
Controls
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
griswold_12_ASD_discovery_controls
Children recruited as pediatric controls from HIHG (Miami, FL) and preterm birth study at Centennial Medical Center (Nashville, TN)
592
Control
Range, preterm-21 yrs.
NA
132718
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
vaags_11_ASD_discovery_controls
Published data from 2,026 healthy individuals from CHOP, 2,493 controls genotyped at the University of Washington; microarray data from 10,603 population-based controls. 1,056 HapMap samples, 4,783 WTCCC controls, and 1,287 SAGE controls
15122
Control
NA
NA
285000
1
0
1
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
asadollahi_14_NDD_discovery_cases
Predominantly European
Array SNP
Affymetrix 6.0, Affymetrix Cytogenetics 2.7, Affymetrix CytoScan HD
HMM
Affymetrix ChAS v.1.0.1
MLPA
bena_13_ASD/DD/ID_discovery_cases
N/A
aCGH, array SNP, solid phase hybridization
Agilent 244K, Agilent 105K, Agilent 180K, OGT custom design 180K, Affymetrix 250K NspI, Affymetrix 250K, Affymetrix Cyto-2.7 M, Illumina 12-330K
FISH and aCGH
brandler_18_ASD_replication_cases
N/A
WGS
Illumina HiSeq X10
ForestSV, Lumpy, Manta, Mobster, SV2
None
gai_11_ASD_discovery_cases
European
Solid phase hybridization
Illumina Infinium II HumanHap550 BeadChip
BeadStudio 3.0
None
griswold_12_ASD_discovery_cases
Range of self-reported ethnicities (specifics NA)
Solid phase hybridization
Illumina Human 1M-v1_C BeadChip, Illumina 1M-DuoV3 BeadChip
Penn CNV, QuantiSNP
BeadStudio
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
yuan_18_ASD/ADHD/ID_discovery_cases
Chinese
Array SNP
Affymetrix CytoScan 750K
Affymetrix ChAS
None
Controls
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
griswold_12_ASD_discovery_controls
Caucasian
Solid phase hybridization
Illumina Human 1M-v1_C BeadChip, Illumina 1M-DuoV3 BeadChip
Penn CNV, QuantiSNP
BeadStudio
kaminsky_11_DD/ID/ASD_discovery_controls
NA
aCGH
Agilent 44K, Agilent 105K
Feature Extraction, DNA Analytics
vaags_11_ASD_discovery_controls
Predominantly European
N/A
N/A
N/A
Cases
Patient ID
Author, Year
Age
Gender
Primary Diagnosis
Clinical Profile
Cognitive Profile
CNV Start
CNV End
CNV Size
Genome Build
Type Method
Validation
asadollahi_14_NDD_discovery_cases-case48459
7 yrs.
M
Learning difficulties
Mild learning difficulties, motor problems, facial dysmorphic features, dilated cardiomyopathy, anal atresia
78785773
79248579
462807
GRCh38
Deletion
Yes
bena_13_ASD/DD/ID_discovery_cases-case3
12 yrs.
F
ASD and intellectual disability
Motor developmental delay, language delay, seizures, dysmorphic features, growth -2.5 SD, OFC -2.2 SD, hyperactivity, Angelman-like symptoms
Moderate developmental delay, intellectual disability
78863904
79163904
300001
GRCh38
Deletion
Yes
brandler_18_ASD_replication_cases-caseAU4013301
N/A
F
ASD
Case from MSSNG cohort
78832547
78835297
2751
GRCh38
Deletion
No
brandler_18_ASD_replication_cases-caseAU4013302
N/A
M
ASD
Case from MSSNG cohort
78832547
78835297
2751
GRCh38
Deletion
No
brandler_18_ASD_replication_cases-caseAU4013303
N/A
M
ASD
Case from MSSNG cohort
78832547
78835297
2751
GRCh38
Deletion
No
brandler_18_ASD_replication_cases-caseAU4093301
N/A
F
ASD
Case from MSSNG cohort
78761917
79051345
289429
GRCh38
Deletion
No
brandler_18_ASD_replication_cases-caseAU4093302
N/A
F
ASD
Case from MSSNG cohort
78761917
79051345
289429
GRCh38
Deletion
No
brandler_18_ASD_replication_cases-caseAU4093304
N/A
F
ASD
Case from MSSNG cohort
78761917
79051345
289429
GRCh38
Deletion
No
gai_11_ASD_discovery_cases-AU1227304
Autism
78385349
78459898
74550
Unknown
Deletion
No
griswold_12_ASD_discovery_cases-case7484
NA
NA
ASD/autism
NA
NA
78837409
78970127
132719
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002349
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
75489052
79610332
4121281
GRCh38
Deletion
Yes
yuan_18_ASD/ADHD/ID_discovery_cases-caseF001
7 yrs.
M
ASD, ADHD, and intellectual disability
Case was initially diagnosed with ASD after clinical assessment at 2 years 5 months; reassessment at 3 years 8 months confirmed that he met the clinical diagnostic criteria for autism based on ABC, CARS, and Modified Checklist for Autism in Toddlers Revised. Birth/neonatal history: uneventful pregnancy and delivery at 38 weeks of gestation; birth weight of 3.2 kg (40th %ile), length of 51 cm (65th %ile), and head circumference of 34.2 cm (40th %ile); Apgar scores all 9. Developmetnal milestones: motor delay (raised head at 4 months, sat alone at 1 year, walking independently at 2 years); significantly delayed language development (only developed two-word sentences). Behavioral/psychiatric evaluation: ADHD; poor eye contact, social difficulties, stereotyped behaviors, repetitive interests; aggressive behavior, depression, anxiety. Brain imaging: normal. Dysmorphic features: high forehead, flat facial profile, auricle dysplasia, widely spaced eyes, blepharophosis, flat nasal bridge, long and broad philtrum, dental dysplasia, micrognathia, sparse eyebrows and hair. Growth parameters: weight of 24 kg (60th %ile), height of 121.8 cm (45th %ile), and head circumference of 51.4 cm (45th %ile) at age of 7 years. Family history: parents were non-consanguineous; the proband's younger brother and father were both healthy and negative for the NRXN3 deletion; the proband's mother was positive for the NRXN3 deletion and presented with language delay, learning difficulties, anxiety, slightly impaired socialization skills, and communication difficulties; the proband's maternal grandmother and maternal aunt were unaffected and negative for NRXN3 deletion; the proband's maternal grandfather was positive for the NRXN3 deletion and presented with language delay, mild impairments in communication and social interaction, schizophrenia, temper tantrums, aggressive behavior, and anxiety in unfamiliar situations.
Moderate intellectual disability (IQ 50, Wechsler Intelligence Scale)
78791924
79014395
222472
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
vaags_11_ASD_discovery_controls-control3
NA
F
Control
Control from Study of Addiction: Genetics and Environment (SAGE) consortium
NA
NA
285000
Unknown
Deletion
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
asadollahi_14_NDD_discovery_cases-case48459
MLPA
Paternal
Unknown
Unknown
NRXN3
bena_13_ASD/DD/ID_discovery_cases-case3
FISH and aCGH
De novo
Unknown
Possibly segregated
NRXN3
brandler_18_ASD_replication_cases-caseAU4013301
No validation step reported
Paternal
NRXN3
brandler_18_ASD_replication_cases-caseAU4013302
No validation step reported
Paternal
NRXN3
brandler_18_ASD_replication_cases-caseAU4013303
No validation step reported
Paternal
NRXN3
brandler_18_ASD_replication_cases-caseAU4093301
No validation step reported
Paternal
NRXN3
brandler_18_ASD_replication_cases-caseAU4093302
No validation step reported
Paternal
NRXN3
brandler_18_ASD_replication_cases-caseAU4093304
No validation step reported
Paternal
NRXN3
gai_11_ASD_discovery_cases-AU1227304
Inherited
NRXN3
griswold_12_ASD_discovery_cases-case7484
qPCR
Maternal
Simplex
Not segregated
NRXN3
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002349
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
RNA5SP387,ERG28,TGFB3-AS1,CYCSP1,RPSAP3,VASH1-AS1,RPL22P2,RN7SKP17,LINC01629,RN7SL356P,IRF2BPL,FAM204DP,MIR1260A,GSTZ1,RN7SL587P,COX6CP11,RPL21P10,ZMYND19P1,C14orf178,FXNP1,RNA5SP388,RPS26P48,BATF,TGFB3,VASH1,LRRC74A,LINC02288,CIPC,ZDHHC22,NGB,POMT2,TMED8,SAMD15,NOXRED1,VIPAS39,ISM2,ALKBH1,FLVCR2,TTLL5,IFT43,GPATCH2L,ESRRB,ANGEL1,LINC02289,TMEM63C,AHSA1,SLIRP,SNW1,ADCK1,SPTLC2,NRXN3
yuan_18_ASD/ADHD/ID_discovery_cases-caseF001
No validation reported
Maternal
Maternal
Multi-generational
Segregated
NRXN3
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
vaags_11_ASD_discovery_controls-control3
NRXN3
No Animal Model Data Available