21q22.13-q22.2CNV Type: Deletion
Largest CNV size: 1236646 bp
Statistics Box:
Number of Reports: 3
Number of Reports: 3
Summary Information
Rare singleton deletion within this region was found in a case from a study of 15,749 individuals from the International Standards for Cytogenomic Arrays (ISCA) consortium with unexplained developmental delay, intellectual disability, dysmorphic features, multiple congenital anomalies, autism spectrum disorders, or clinical features suggestive of a chromosomal syndrome (Kaminsky et al., 2011).
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
DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies.
Deletion
Minor Reports
Title
Author, Year
Report Class
CNV Type
Integrative approach to interpret DYRK1A variants, leading to a frequent neurodevelopmental disorder
Deletion
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
courraud_21_DD/ID/EP_discovery_cases
individuals with de novo deletions affecting the DYRK1A gene.
3
All three individuals presented with epilepsy/seizures; two individuals also presented with developmental delay and intellectual disability.
Range, 0.5-10 yrs.
66.67% Male
1739652
2
0
2
ji_15_DD/ID/EP/ASD_discovery_cases
Cases with microdeletions of chromosome 21q22.12-q22.3 that include the DYRK1A gene; three unrelated sporadic cases, two familial cases (affected siblings)
5
All five cases present with global developmental delay and/or intellectual disability; four cases present with epilepsy/seizures, and one case with ASD
Range, 17 mos.-5 yrs. 8 mos.
60.00% Male
4170000
4
0
4
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
1236646
1
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
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
courraud_21_DD/ID/EP_discovery_cases
N/A
aCGH
N/A
N/A
N/A
None
ji_15_DD/ID/EP/ASD_discovery_cases
2 Caucasian, 1 European, 1 Hispanic, 1 Polish
aCGH, array SNP
BlueGnome CytoChip ISCA 8x60K v2.0, Affymetrix 6.0, Spectral Genomic CC v4.0
FISH
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
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
Cases
Patient ID
Author, Year
Age
Gender
Primary Diagnosis
Clinical Profile
Cognitive Profile
CNV Start
CNV End
CNV Size
Genome Build
Type Method
Validation
courraud_21_DD/ID/EP_discovery_cases-case1
10 yrs.
M
Developmental delay, intellectual disability, and epilepsy/seizures
Birth/neonatal history: intrauterine growth retardation. Developmental milestones: motor delay, delayed ability to walk (19.5 months). Language and communication evaluation: absent speech. Motor and musculoskeletal evaluation: hyperreflexia. Behavioral/psychiatric evaluation: anxiety, additional behavioral problems. Epilepsy/seizures: a history of tonic-clonic seizures. Brain imaging: enlarged ventricles, and cortical or subcortical atrophy. Additional medical history: thin skin, dermatitis, inguinal hernia, pyloric stenosis, feeding difficulties (feeding difficulties in infancy, then food selection). Growth parameters: decreased body weight (-3.2 SD), microcephaly (OFC <-4 SD).
Moderate intellectual disability
37109503
38818534
1709032
GRCh38
Deletion
No
courraud_21_DD/ID/EP_discovery_cases-case40
8.5 yrs.
M
Developmental delay, intellectual disability, epilepsy/seizures, and stereotypy
Birth/neonatal history: intrauterine growth retardation. Developmental milestones: motor delay, delayed ability to walk (28 months). Language and communication evaluation: absent speech. Motor and musculoskeletal evaluation: pyramidal signs. Behavioral/psychiatric evaluation: stereotypies, anxiety, sleep disorder, a fascination with water, additional behavioral problems. Epilepsy/seizures: a history of seizures (febrile seizures, tonic-clonic seizures). Brain imaging: hypoplasia of the corpus callosum, enlarged cistern. Additional medical history: thin skin, nail dystrophy, hypolasia of the optic nerve, papillary pallor, feeding difficulties (poor eating). Growth parameters: microcephaly (OFC -6 SD.
Severe intellectual disability
36929839
38669490
1739652
GRCh38
Deletion
No
ji_15_DD/ID/EP/ASD_discovery_cases-patient10
5 yrs. 8 mos.
F
Developmental delay/intellectual disability and seizures
Birth/neonatal history: IUGR; birth OFC -4 SD, birth length -4 SD, birth weight -4 SD;feeding difficulties during infancy. Developmental milestones: global developmental delay, severe speech delay. Motor and musculoskeletal evaluation: abnormal gait/ataxia; skeletal anomalies. Behavioral/psychiatric evaluation: happy demeanor. Epilepsy/seizures: yes. Brain imaging: brain abnormalities detected on MRI. Dysmorphic features: yes. Growth parameters: microcephaly; OFC -2 SD, length 10th %ile, and weight 10th %ile at time of last follow-up. Family history: similarly affected sibling (positive for 21q22.13-q22.2 deletion); mother carries a balanced intrachromosal insertion on chr21.
Intellectual disability
37368802
38902182
1533381
GRCh38
Deletion
Yes
ji_15_DD/ID/EP/ASD_discovery_cases-patient11
2 yrs. 3 mos.
M
Developmental delay/intellectual disability and seizures
Birth/neonatal history: IUGR; birth OFC -3 SD, birth length -3 SD, birth weight -3 SD; feeding difficulties during infancy. Developmental milestones: global developmental delay, severe speech delay. Motor and musculoskeletal evaluation: not walking yet; skeletal anomalies. Behavioral/psychiatric evaluation: normal. Epilepsy/seizures: yes. Brain imaging: brain abnormalities detected on MRI. Dysmorphic features: yes; strabismus. Growth parameters: microcephaly; OFC -4 SD, length 3rd-10th %ile, and weight 3rd-10th %ile at time of last follow-up. Family history: similarly affected sibling (positive for 21q22.13-q22.2 deletion); mother carries a balanced intrachromosal insertion on chr21.
Intellectual disability
37368802
38902182
1533381
GRCh38
Deletion
Yes
ji_15_DD/ID/EP/ASD_discovery_cases-patient13
17 mos.
F
Developmental delay/intellectual disability
Birth/neonatal history: IUGR; birth OFC -2 SD, birth length -2 SD, birth weight -2 SD;feeding difficulties during infancy. Developmental milestones: global developmental delay, severe speech delay. Motor and musculoskeletal evaluation: skeletal anomalies. Behavioral/psychiatric evaluation: N/A. Epilepsy/seizures: none reported. Brain imaging: N/A. Additional medical history: bilateral cataracts, GERD. Dysmorphic features: yes. Growth parameters: microcephaly; OFC -2 SD, length -1 SD, and weight -3 SD at time of last follow-up.
Intellectual disability
36467112
40055599
3588488
GRCh38
Deletion
Yes
ji_15_DD/ID/EP/ASD_discovery_cases-patient14
5 yrs.
M
ASD, developmental delay/intellectual disability, and seizures
Case present in DECIPHER (252136). Birth/neonatal history: birth OFC -4 SD, birth length normal, birth weight -3 SD; feeding difficulties during infancy. Developmental milestones: global developmental delay, severe speech delay. Motor and musculoskeletal evaluation: abnormal gait/ataxia. Behavioral/psychiatric evaluation: ASD, hand stereotypies. Epilepsy/seizures: yes. Brain imaging: brain abnormalities detected on MRI. Additional medical history: unilateral inguinal hernia. Dysmorphic features: yes; strabismus. Growth parameters: microcephaly; OFC -5 SD, length -2 SD, and weight -2 SD at time of last follow-up.
Intellectual disability
37244417
41411667
4167251
GRCh38
Deletion
Yes
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002659
NA
NA
Developmental delay/intellectual disability/ASD
Clinical profile NA
Cognitive profile NA
37408770
38645794
1237025
GRCh38
Deletion
Yes
Controls
No Control Data Available
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
courraud_21_DD/ID/EP_discovery_cases-case1
De novo
ERG,ETS2,DYRK1A,DSCR8,DSCR10,DSCR9,LINC00114,KCNJ6,KCNJ15,TTC3-AS1,SNRPGP13,SPATA20P1,DSCR4-IT1,LINC01423,KCNJ6-AS1,TTC3,RN7SL678P,VPS26C,DSCR4
courraud_21_DD/ID/EP_discovery_cases-case40
De novo
ERG,DYRK1A,PIGP,RIPPLY3,DSCR8,HLCS,DSCR10,DSCR9,MRPL20P1,DPRXP5,KCNJ6,KCNJ15,TTC3-AS1,SNRPGP13,SPATA20P1,DSCR4-IT1,LINC01423,KCNJ6-AS1,TTC3,RNU6-696P,RN7SL678P,VPS26C,DSCR4
ji_15_DD/ID/EP/ASD_discovery_cases-patient10
FISH
Maternal
Multiplex
Segregated
KCNJ6-AS1,DSCR4-IT1,SPATA20P1,LINC01423,SNRPGP13,LINC00114,RPSAP64,DSCR10,ETS2,DYRK1A,DSCR4,DSCR8,KCNJ15,ERG,KCNJ6
ji_15_DD/ID/EP/ASD_discovery_cases-patient11
FISH
Maternal
Multiplex
Segregated
KCNJ6-AS1,DSCR4-IT1,SPATA20P1,LINC01423,SNRPGP13,LINC00114,RPSAP64,DSCR10,ETS2,DYRK1A,DSCR4,DSCR8,KCNJ15,ERG,KCNJ6
ji_15_DD/ID/EP/ASD_discovery_cases-patient13
FISH
De novo
Simplex
Likely segregated
HLCS-IT1,RNA5SP491,DPRXP5,RNU6-696P,DSCR9,RN7SL678P,KCNJ6-AS1,DSCR4-IT1,SPATA20P1,LINC01423,SNRPGP13,LINC00114,RPSAP64,RPL23AP12,PCBP2P1,PSMG1,TIMM9P2,BRWD1-IT1,METTL21AP1,BRWD1-AS2,HMGN1,RNF6P1,MIR6508,MYL6P2,RPS26P4,PSMD4P1,MRPL20P1,RIPPLY3,PIGP,TTC3-AS1,DSCR10,ETS2,LINC01700,WRB,LCA5L,B3GALT5-AS1,IGSF5,PCP4,CLDN14,HLCS,TTC3,VPS26C,DYRK1A,DSCR4,DSCR8,KCNJ15,ERG,BRWD1,BRWD1-AS1,WRB-SH3BGR,SH3BGR,B3GALT5,DSCAM,SIM2,KCNJ6
ji_15_DD/ID/EP/ASD_discovery_cases-patient14
FISH
De novo
Simplex
Likely segregated
KCNJ6-AS1,DSCR4-IT1,SPATA20P1,LINC01423,SNRPGP13,LINC00114,RPSAP64,RPL23AP12,PCBP2P1,PSMG1,TIMM9P2,BRWD1-IT1,METTL21AP1,BRWD1-AS2,HMGN1,RNF6P1,MIR6508,MYL6P2,RPS26P4,MIR4760,DSCAM-AS1,YRDCP3,LINC00323,MIR3197,PLAC4,BACE2-IT1,DSCR10,ETS2,LINC01700,WRB,LCA5L,B3GALT5-AS1,IGSF5,PCP4,DSCAM-IT1,BACE2,FAM3B,MX2,VPS26C,DYRK1A,DSCR4,DSCR8,KCNJ15,ERG,BRWD1,BRWD1-AS1,WRB-SH3BGR,SH3BGR,B3GALT5,DSCAM,KCNJ6
kaminsky_11_DD/ID/ASD_discovery_cases-ISCA00002659
FISH, qPCR, MLPA, aCGH, or standard G-banded chromosome analysis
De novo
Unknown
Unknown
KCNJ6-AS1,DSCR4-IT1,SPATA20P1,LINC01423,SNRPGP13,DSCR10,DYRK1A,DSCR4,DSCR8,KCNJ15,ERG,KCNJ6
Controls
No Control Data Available
No Animal Model Data Available