1p21.3-p21.2CNV Type: Deletion
Largest CNV size: 1625209 bp
Statistics Box:
Number of Reports: 8
Number of Reports: 8
Summary Information
A de novo deleton within this region was identified in a female ASD proband from SSC quad family 13346 (Krumm et al., 2013).
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.
Deletion-Duplication
Performance of case-control rare copy number variation annotation in classification of autism.
Deletion
Association of new deletion/duplication region at chromosome 1p21 with intellectual disability, severe speech deficit and autism spectrum disorder-...
Duplication
Minor Reports
Title
Author, Year
Report Class
CNV Type
Large-scale discovery of novel genetic causes of developmental disorders.
Deletion
Clinical Targeted Panel Sequencing Analysis in Clinical Evaluation of Children with Autism Spectrum Disorder in China
Duplication
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
brecevic_17_ID/PDD_discovery_cases
Fifth child of parents with borderline IQ or mild intellectual disability presenting with a small supernumerary marker (sSMC) derived from chromosome 1p21.3-p21.2
1
Case diagnosed at age of 8 years with moderate-to-severe intellectual disability (ID), pervasive developmental disorder (PDD) with elements of autism spectrum disorder, undeveloped speech, febrile convulsions, and nocturnal enuresis
19 yrs.
Male
3560000
0
1
1
engchuan_15_ASD_discovery_cases
Samples from the Autism Genome Project (AGP)
1892
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
N/A
85.78% Male
2748330
1
0
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
2812916
1
0
1
hu_22_ASD_discovery_cases
Patients receiving a diagnosis of ASD in the Department of Child Health Care, Children's Hospital of Fudan University, that were included consecutively from January 2019 to December 2020.
573
Cases met criteria for autism spectrum disorder (ASD) using DSM-5 criteria.
Range, 16 mos.-12.8 yrs. (mean, 3.6 yrs)
80.1% Male
3172094
0
1
1
krumm_13_ASD_discovery_cases
Probands from quad families ascertained as part of the Simons Simplex Collection (SSC); CNVs detected using data from four previously published exome sequencing studies (O'Roak et al., 2011; Iossifov et al., 2012; O'Roak et al., 2012; Sanders et al., 2012)
411
Diagnosis of ASD. Social Responsiveness Scale (SRS) used as a quantitative measure of social deficits
N/A
81.265% Male
1625209
1
0
1
krumm_15_ASD_discovery_cases
Probands from the Simons Simplex Collection
2377
Diagnosis of ASD
N/A
N/A
1625209
1
0
1
li_23_DD/ID_discovery_cases
Patient from Jiangxi Province, China, with a de novo 1p21.3-p21.2 deletion containing only one coding gene (PLPPR4).
1
Patient presented with developmental delay (Gesell Developmental Schedules score of 59), mild intellectual disability (IQ 46 on the China-Wechsler Intelligence Scale), and autistic behavior.
15 yrs.
Female
213878
1
0
1
pinto_14_ASD_discovery_cases
ASD probands from simplex and multiplex families collected as part of stage 2 of the Autism Genome Project (AGP) after quality control (1,604 before QC)
1359
Cases classified according to ADOS and ADI-R
N/A
N/A
2748331
1
1
2
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
0
0
0
0
krumm_13_ASD_discovery_controls
Unaffected siblings of ASD probands from quad families ascertained as part of the Simons Simplex Collection (SSC); CNVs detected using data from four previously published exome sequencing studies (O'Roak et al., 2011; Iossifov et al., 2012; O'Roak et al., 2012; Sanders et al., 2012)
411
Control (unaffected siblings of ASD probands). Social Responsiveness Scale (SRS) used as a quantitative measure of social deficits
N/A
46.47% Male
0
0
0
0
krumm_15_ASD_discovery_controls
Unaffected siblings from quad families from the Simons Simplex Collection
1786
Control
N/A
N/A
0
0
0
0
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
brecevic_17_ID/PDD_discovery_cases
European
G-banded karyotyping, MLPA
MRC-Holland MLPA probe sets (SALSA MLPA Lits P036-Human Telomere, P070-Human Telomere, P245-Microdeletion Syndromes-1, P297-Microdeletion Syndromes-2, P343-B1 Autism and ME028-PWS/AS)
Gene Marker (Soft Genetics)
FISH, aCGH
engchuan_15_ASD_discovery_cases
Caucasian
Solid phase hybridization
Illumina 1M
Yes
fitzgerald_14_ASD/DD/ID_discovery_cases
UK and Ireland
aCGH, WES
Agilent 2x1M, Agilent Exome+
Cnsolidate, CoNVex
None
hu_22_ASD_discovery_cases
China
Targeted gene panel sequencing
Illumina HiSeq X10
CANOES, HMZDelFinder
PICNIC, AnnotSV
None
krumm_13_ASD_discovery_cases
N/A
WES
Whole exome sequencing platforms used in four recent publications (O'Roak et al., 2011; Sanders et al., 2012; O'Roak et al., 2012, and Iossifov et al., 2012)
DNACopy, CGHCall
CoNIFER
Solid phase hybridization (Illumina 1M), aCGH (Agilent SurePrint G3 4x180K), or confirmed by manual inspection
krumm_15_ASD_discovery_cases
N/A
WES
CoNIFER, XHMM
Solid phase hybridization (Illumina 1M, 1 M Duo, or Omni 2.5)
li_23_DD/ID_discovery_cases
China
CMA
NA
NA
NA
None
pinto_14_ASD_discovery_cases
Predominantly European
Solid phase hybridization
Illumina 1M (v.1 and v.3)
qPCR, MLPA, long-range PCR
Controls
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
engchuan_15_ASD_discovery_controls
Caucasian
Solid phase hybridization
Illumina 1M
None
krumm_13_ASD_discovery_controls
N/A
WES
Whole exome sequencing platforms used in four recent publications (O'Roak et al., 2011; Sanders et al., 2012; O'Roak et al., 2012, and Iossifov et al., 2012)
DNACopy, CGHCall
CoNIFER
None
krumm_15_ASD_discovery_controls
N/A
WES
CoNIFER, XHMM
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
brecevic_17_ID/PDD_discovery_cases-case1
19 yrs.
M
Intellectual disability and pervasive developmental disorder
Case diagnosed at age of 8 years with moderate-to-severe intellectual disability, pervasive developmental disorder with elements of autism spectrum disorder, undeveloped speech, febrile convulsions, and nocturnal enuresis. Birth/neonatal history: born at term after uneventful pregnancy. Developmental milestones: unremarkable early motor development; severely delayed language development. Language and communication evaluation: speech is sparse and imcomprehensible (at the word level) with echolalia and neologisms. Motor and musculoskeletal evaluation: sloping and dropped shoulders; mild thoracic kyphosis (with a hump resembling a buffalo hump) extending to lumbar lordosis; long and tapering fingers with bilateral clinodactyly of the 5th finger; very high and rigid instep; first toe is long and widely spaced from the 2nd toe; partial subcutaneous syndactyly of 2nd and 3rd toes; apparently pointed toes; peculiar gait with tendency woard toe-walking (most evident when running). Behavioral/psychiatric evaluation: autistic features, behavioral problems and hyperactivity noted at 2 years, which became more remarkable from 6 years; psychomotor restlessness; patient is disoriented, social unadapted, with very poor concentration and attention; aggressive outbursts. Epilepsy/seizures: hospitalized for febrile convulsions in 2nd and 3 year of life. Additional medical history: nocturnal enuresis. Dysmorphic features: deep-set eyes, hooded eyelids, philtrum with upturned upper lip, open mouth appearance, narrow and high-arched palate, maxillary prognathism, unilateral cryptorchidism. Growth parameters: height of 172 cm (25th %ile), weight of 60 kg (20th %ile), and head circumference of 55 cm (25th %ile) at 19 years. Family history: fifth child of parents who both function at borderline intellectual level or mild intellectual disability (boy and siblings were placed in foster care homes, as parents had not been able to care for them). Additional genetic information: 1p21.3-p21.2 duplication is present as a small supernumerary marker chromosome (sSMC) present in 80% of patient lymphocytes.
Moderate-to-severe intellectual disability
95954683
99515786
3561104
GRCh38
Duplication
Yes
engchuan_15_ASD_discovery_cases-case8658_201
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
97937478
100685808
2748331
GRCh38
Deletion
Yes
fitzgerald_14_ASD/DD/ID_discovery_cases-DECIPHER260349
N/A
M
Learning disability
Specific learning disability; Precocious puberty
96535193
99348109
2812917
GRCh38
Deletion
No
hu_22_ASD_discovery_cases-case12
NA
M
ASD
Case met criteria for ASD using DSM-5.
97077741
100249834
3172094
GRCh38
Duplication
No
krumm_13_ASD_discovery_cases-case13346.p1
N/A
F
ASD
ASD proband from SSC quad family 13346. SRS score of 84.
Full-scale IQ (FSIQ) score of 59.
98893071
100518280
1625210
GRCh38
Deletion
Yes
krumm_15_ASD_discovery_cases-case13346.p1
N/A
Female
ASD
Proband from the Simons Simplex Collection (SSC). Family type: Quad
98893071
100518280
1625210
GRCh38
Deletion
Yes
li_23_DD/ID_discovery_cases-case1
15 yrs.
F
Developmental delay, intellectual disability, and autistic features
Birth/neonatal history: premature birth with birth weight less than 2 kg. Developmental milestones: developmental delay (Gesell Developmental Schedules score of 59), language and motor delay. Language and communication evaluation: poor expression ability, poor social communication. Motor and musculoskeletal evaluation: uncoordinated walking, difficulty walking in a straight ine, inability to walk with small steps, tendency to fall when turning and backward, clumsiness (heel-knee-tibia test of both lower limbs), hypomyotonia. Behavioral/psychiatric evaluation: aggressive behavior (hair grabbing, needle pricking) when younger, autistic behavior. EEG: slowing of alpha rhythm of video EEG. Visual evaluation: left exotropia, poor bilateral eye convergence, optic nerve atrophy, irregularly reduced visual field sensitivity in the left eye. Dysmorphic features: dysmorphic features included hypertelorism and strabismus.
Mild intellectual disability (IQ 46 on the China-Wechsler Intelligence Scale), poor mathematical skills (cannot add or subtract).
99115355
99329232
213878
GRCh38
Deletion
No
pinto_14_ASD_discovery_cases2-case8658_201
N/A
F
ASD
Autism on ADI-R and ADOS, comorbid ADHD, no language delay; overweight, height and head circumference 50th %ile, high pain tolerance, no epilepsy. Family history: father healthy; mother with hyperthyroidism; two healthy siblings (not tested).
Low-average IQ (WASI at 21 y: VIQ 78, PIQ 88, FSIQ 81)
97937478
100685808
2748331
GRCh38
Deletion
Yes
pinto_14_ASD_discovery_cases2-case9877_204
N/A
M
ASD
Autism (autism on ADI-R and ADOS), language delay (first words 36 mo, first phrases 60 mo), functional language, normal height and head circumference, weight 1.6 SD, no dysmorphic features, normal physical exam, no epilepsy. Family history: both parents are healthy; three siblings (not tested).
Mild ID (WISC-R at 11 y: VIQ 51, PIQ 80, FSIQ 64)
98009211
99407416
1398206
GRCh38
Duplication
Yes
Controls
No Control Data Available
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
brecevic_17_ID/PDD_discovery_cases-case1
FISH, aCGH
Possibly either or both parents
Unknown
Multi-generational
Unknown
RNU1-130P,UBE2WP1,EEF1A1P11,RN7SL831P,NDUFS5P2,RPL7P9,RN7SKP270,SEC63P1,RPL26P9,DPYD-AS2,MIR2682,MIR137,NFU1P2,DPYD-IT1,LINC01776,PLPPR4,LINC01787,PTBP2,DPYD-AS1,MIR137HG,SNX7,PLPPR5,LINC01708,DPYD
engchuan_15_ASD_discovery_cases-case8658_201
De novo
MIR2682,MIR137,NFU1P2,HMGB3P10,RNU4-75P,RNU6-750P,RNU6-1318P,RPL23AP90,BRI3P1,MIR553,BCAS2P2,GPR88,LINC01776,PLPPR4,PALMD,MFSD14A,SASS6,LRRC39,DBT,RTCA-AS1,LINC01349,MIR137HG,SNX7,PLPPR5,LINC01708,FRRS1,AGL,SLC35A3,TRMT13,RTCA,CDC14A,DPYD
fitzgerald_14_ASD/DD/ID_discovery_cases-DECIPHER260349
De novo
Multi-generational
Not segregated
RN7SL831P,NDUFS5P2,RPL7P9,RN7SKP270,SEC63P1,RPL26P9,DPYD-AS2,MIR2682,MIR137,NFU1P2,DPYD-IT1,LINC01776,PLPPR4,PTBP2,DPYD-AS1,MIR137HG,SNX7,PLPPR5,DPYD
hu_22_ASD_discovery_cases-case12
Unknown
AGL,DPYD,DBT,SNX7,PALMD,TRMT13,MFSD14A,LRRC39,PLPPR5,SASS6,MIR137HG,FRRS1,MIR137,BRI3P1,LINC01776,HMGB3P10,NFU1P2,RPL26P9,SEC63P1,MIR2682,DPYD-IT1,DPYD-AS2,DPYD-AS1,LINC01708,RNU6-750P,RNU4-75P,RNU6-1318P,RPL23AP90,PLPPR4,SLC35A3
krumm_13_ASD_discovery_cases-case13346.p1
Solid phase hybridization (Illumina 1M) or aCGH (Agilent SurePrint G3 4x180K)
De novo
Simplex
Segregated
HMGB3P10,RNU4-75P,RNU6-750P,RNU6-1318P,RPL23AP90,BRI3P1,MIR553,BCAS2P2,PLPPR4,PALMD,MFSD14A,SASS6,LRRC39,DBT,RTCA-AS1,PLPPR5,LINC01708,FRRS1,AGL,SLC35A3,TRMT13,RTCA,CDC14A
krumm_15_ASD_discovery_cases-case13346.p1
1M-Duov3
De novo
Simplex
Segregated
HMGB3P10,RNU4-75P,RNU6-750P,RNU6-1318P,RPL23AP90,BRI3P1,MIR553,BCAS2P2,PLPPR4,PALMD,MFSD14A,SASS6,LRRC39,DBT,RTCA-AS1,PLPPR5,LINC01708,FRRS1,AGL,SLC35A3,TRMT13,RTCA,CDC14A
li_23_DD/ID_discovery_cases-case1
De novo
Simplex
PLPPR4
Neurons from patient-derived iPSCs showed reduced expression of PLPPR4 and MAP2 and increased expres
pinto_14_ASD_discovery_cases2-case8658_201
qPCR
De novo
Simplex
Likely segregated (2 healthy siblings, not tested)
MIR2682,MIR137,NFU1P2,HMGB3P10,RNU4-75P,RNU6-750P,RNU6-1318P,RPL23AP90,BRI3P1,MIR553,BCAS2P2,GPR88,LINC01776,PLPPR4,PALMD,MFSD14A,SASS6,LRRC39,DBT,RTCA-AS1,LINC01349,MIR137HG,SNX7,PLPPR5,LINC01708,FRRS1,AGL,SLC35A3,TRMT13,RTCA,CDC14A,DPYD
pinto_14_ASD_discovery_cases2-case9877_204
qPCR
De novo
Simplex
Likely segregated (3 siblings, not tested)
MIR2682,MIR137,NFU1P2,LINC01776,PLPPR4,MIR137HG,SNX7,PLPPR5
Controls
No Control Data Available
No Animal Model Data Available