Xp11.4-p11.3CNV Type: Deletion
Largest CNV size: 3500000 bp
Statistics Box:
Number of Reports: 5
Number of Reports: 5
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-Duplication
Minor Reports
Title
Author, Year
Report Class
CNV Type
Interpretation of clinical relevance of X-chromosome copy number variations identified in a large cohort of individuals with cognitive disorders an...
Deletion
Large-scale discovery of novel genetic causes of developmental disorders.
Deletion
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
catino_22_DD/ID/EP_discovery_cases
Unrelated patients harboring Xp11.4-p11.3 copy number variation affecting the USP9X, DDX3X, CASK, and MAOA genes.
2
Both cases presented with developmental delay and intellectual disability; one case also presented with epilepsy/seizures.
Range, 26-31 yrs.
50% Male
3874135
1
1
2
digregorio_17_DD/ID_discovery_cases
Consecutive cases examined in the Medical Genetics Unit at the "Citta della Salte e della Scienza" University Hospital (Turin, Italy) from 2008 to 2014 (cases with CNVs are present in DECIPHER database)
1015
Cases diagnosed with idiopathic developmental delay and/or intellectual disability (DD/ID)
N/A
N/A
689000
0
1
1
fitzgerald_14_ASD/DD/ID_discovery_cases
Children recruited through all 24 regional genetics services of the UK National Health Service and Republic of Ireland as part of the Deciphering Developmental Disorders Study
1133
Cases affected by severe, undiagnosed developmental disorders; most common phenotypes include developmental delay, intellectual disability, specific learning disability, autism, seizures, microcephaly, and dysmorphic features.
Median age, 5.5 years
N/A
2095549
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
2416481
1
1
2
willemsen_12_DD/ID_discovery_cases
Individuals referred between Jan. 2003 and August 2010 to diagnostic center at Dept. of Human Genetics, Radboud Univ. Mijmegen Medical Centre, Nijmegen, The Netherlands for genome-wide array analysis (emphasis on X chromosome CNVs)
4407
Majority of cases: indication of developmental delay/intellectual disability [with or without other neuropsychiatric disorders (ASD, ADHD, etc.) and/or congenital anomalies]. Minority of cases: congenital anomalies or behavioral problems without DD/ID.
2/3 of cases: age range of 1-18 yrs.
54.5% Male
3500000
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
300628
1
1
2
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
catino_22_DD/ID/EP_discovery_cases
Italy
Solid phase hybridization
Illumina Infinium CytoSNP-850K
NA
BlueFuse Multi v.4.4
RT-PCR, microsatellite analysis
digregorio_17_DD/ID_discovery_cases
Italian
aCGH
Agilent 60K (SurePrint G3 Human CGH Microarray 8x60K)
ADM-2
Agilent CGH Analytics software ver. 4.0.81
None
fitzgerald_14_ASD/DD/ID_discovery_cases
UK and Ireland
aCGH, WES
Agilent 2x1M, Agilent Exome+
Cnsolidate, CoNVex
None
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
willemsen_12_DD/ID_discovery_cases
Netherlands
aCGH, array SNP
Agilent 32K BAC array, Affymetrix 250K
CNAG V2.0 (SNP array)
None
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
catino_22_DD/ID/EP_discovery_cases-case1
26 yrs.
F
Developmental delay, intellectual disability, and epilepsy/seizures
Birth/neonatal history: born at term after an uneventful pregnancy by vaginal delivery with normal Apgar scores; small for gestational age (birth weight <3rd %ile); ostium secundum atrial septal defect, anomalous pulmonary venous return, and partial right bundle branch block diagnosed at birth. Developmental milestones: global developmental delay, especially in language and fine motor skills. Motor and musculoskeletal evaluation: asymmetric thorax, mild left hypomastia, presence of striae on the scapular and pelvic girdle cutis, bilateral four finger line, brachydactyly with short hands (hand length <3rd %ile), hyperlaxity of the interphalangeal joint of the first fingers, minimal cutaneous syndactyly, bilateral flat feet, sandal gap. Behavioral/psychiatric evaluation: psychotic-like crises recorded from late adolescence. Epilepsy/seizures: rare syncopal and collapse episodes with loss of consciousness reported since childhood. EEG: low voltage, not very organized, overall symmetric activity with defined anomalies at 25 years. Brain imaging: multiple gliotic foci of white and gray matter, inferior cerebellar vermis hypotonia, and mega cisterna magna detected on brain MRI at 21 years. Addtional medical history: hypomelanosis of Ito, left inguinal hernia; menarche at 11 years; unilateral myopia, diabetes, fatigability, exertional dyspnea, recurrent frontal migraine, and secondary amenorrhea recorded from late adolescence; dyschromia over the limbs, generalized hypohidrosis. Dysmorphic features: flat occiput, wide forehead, flat facial profile, slight facial asymmetry, light lateral blepharophimosis, short palpebral fissures, hypostomia, micrognathia. Growth parameters: growth failure at 1 year; mildly overweight at 9 years; weight 45.5 kg (10th %ile), height 148.5 cm (<<-2 SD), BMI 20.7, OFC 50.5 cm (<<3rd %ile). Family history: fourth child of healthy non-consanguineous parents.
Intellectual disability
40252459
44126593
3874135
GRCh38
Deletion
RT-PCR, microsatellite analysis
catino_22_DD/ID/EP_discovery_cases-case2
31 yrs.
M
Developmental delay and intellectual disability
Birth/neonatal history: reduced fetal movements recorded during pregnancy; delivery at term with birth weight 3200 kg and normal Apgar scores; neonatal jaundice. Developmental milestones: delayed psychomotor development (head control at 9 months, trunk control at 12 months, first steps at 21 months, sphincter control at 30 months, first words at 36 months). Language and communication evaluation: nasal voice. Motor and musculoskeletal evaluation: lumbar hyperlordosis, drumstick fingers, flat feet, long toes, cutaneous 2-3 syndactyly, scoliosis. Behavioral/psychiatric evaluation: good socialization. Brain imaging: normal brain CT scan at 7 years. Additional medical history: congenital hypertrophic pyloric stenosis, strabismus. Dysmorphic features: protruding upper lip, anteverted nostrils, prominent columella, large and posteriorly rotated ears, tooth abnormalities, ogival palate/cleft palate, upslanting palpebral fissures, hypertelorism, epicanthus, erythema of the face. Growth parameters: postnatal growth retardation due to milk allergy and continuous vomiting; short stature. Family history: third child in a sibship of four born to healthy non-consanguineous parents; family history notable for a history of seizures and cognitive delay in a maternal uncle and tremor in a materal aunt and in the maternal grandmother.
Intellectual disability
40914093
44156268
3242176
GRCh38
Duplication
RT-PCR
digregorio_17_DD/ID_discovery_cases-DECIPHER_299880
N/A
M
Developmental delay/intellectual disability
41981988
42670636
688649
GRCh38
Duplication
No
fitzgerald_14_ASD/DD/ID_discovery_cases-DECIPHER260322
N/A
F
Developmental delay
Pontocerebellar hypoplasia; Progressive microcephaly; Cortical visual impairment; Severe global developmental delay
41787069
43882625
2095557
GRCh38
Deletion
No
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001859
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
41823849
44240337
2416489
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00005209
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
41431518
43256505
1824988
GRCh38
Duplication
Yes
willemsen_12_DD/ID_discovery_cases-case7
2 yrs.
F
Intellectual disability
Microcephaly, facial dysmorphic features
Intellectual disability
42115803
45565811
3450009
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
engchuan_15_ASD_discovery_controls-controlB461757_1007854302
N/A
N/A
Control
No previous psychiatric history
42380397
42681026
300630
GRCh38
Duplication
No
engchuan_15_ASD_discovery_controls-controlHABC_900877_900877
N/A
N/A
Control
No previous psychiatric history
42551792
42646021
94230
GRCh38
Deletion
No
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
catino_22_DD/ID/EP_discovery_cases-case1
De novo
DDX3X,GPR82,NYX,PPP1R2C,IMPDH1P4,CXorf38,YWHAZP10,GPR34,RPS2P55,MPC1L,NANOGP10,RPL32P36,IMPDH1P2,RBM39P1,DPRXP6,CLIC4P3,SHISA5P1,ATP5MC2P4,CLDN7P1,RPS15AP39,MAOB,NDP,MAOA,SDCBPP3,TNIP2P1,GEMIN7P1,RNA5SP502,CASK-AS1,NDP-AS1,MED14OS,PINCR,LINC02601,RN7SL15P,RNU7-164P,RNU6-202P,RNU6-630P,RN7SL144P,RNU6-1124P,RNU6-1321P,SMIM15P1,USP9X,MKRN4P,CASK,ATP6AP2,MED14
CASK and USP9X expression in whole blood similar to controls.
catino_22_DD/ID/EP_discovery_cases-case2
Maternal
DDX3X,GPR82,NYX,PPP1R2C,EFHC2,IMPDH1P4,YWHAZP10,GPR34,RPS2P55,NANOGP10,RBM39P1,CLIC4P3,SHISA5P1,ATP5MC2P4,RPS15AP39,MAOB,NDP,MAOA,GEMIN7P1,RNA5SP502,CASK-AS1,NDP-AS1,PINCR,LINC02601,RN7SL15P,RNU6-202P,RNU6-630P,RN7SL144P,RNU6-1124P,RNU6-1321P,SMIM15P1,USP9X,CASK
CASK and USP9X expression increased by 50% compared to controls.
digregorio_17_DD/ID_discovery_cases-DECIPHER_299880
Maternal
ATP5MC2P4,RNU6-630P,RNU6-1124P
fitzgerald_14_ASD/DD/ID_discovery_cases-DECIPHER260322
De novo
Unknown
Unknown
RNU6-202P,ATP5MC2P4,RNU6-630P,RNU6-1124P,PPP1R2C,IMPDH1P4,NANOGP10,PINCR,MAOA,CASK,MAOB
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00001859
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
De novo
Unknown
Unknown
RNU6-202P,ATP5MC2P4,RNU6-630P,RNU6-1124P,PPP1R2C,IMPDH1P4,NANOGP10,PINCR,MAOA,NDP,NDP-AS1,CASK,MAOB,EFHC2
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00005209
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
Maternal
Unknown
Unknown
CASK-AS1,RNU6-1321P,RN7SL144P,GPR34,RNU6-202P,ATP5MC2P4,RNU6-630P,RNU6-1124P,PPP1R2C,NYX,GPR82,PINCR,CASK
willemsen_12_DD/ID_discovery_cases-case7
De novo
RNU6-630P,RNU6-1124P,PPP1R2C,IMPDH1P4,NANOGP10,RRM2P3,FDPSP5,CHTF8P1,RPL19P20,RPSAP61,RN7SL291P,DUSP21,PINCR,MAOA,NDP,NDP-AS1,TATDN2P1,FUNDC1,MAOB,EFHC2,LINC01204,KDM6A
Controls
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
engchuan_15_ASD_discovery_controls-controlB461757_1007854302
Unknown
engchuan_15_ASD_discovery_controls-controlHABC_900877_900877
Unknown
No Animal Model Data Available