16q23.2-q23.3CNV Type: Deletion
Largest CNV size: 1590000 bp
Statistics Box:
Number of Reports: 2
Number of Reports: 2
Summary Information
De novo 16q23.2-q23.3 deletions involving the CMIP gene were identified in two unrelated individuals diagnosed with ASD and ADHD (Luo et al., 2017).
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
CMIP haploinsufficiency in two patients with autism spectrum disorder and co-occurring gastrointestinal issues.
Deletion
Minor Reports
Title
Author, Year
Report Class
CNV Type
Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder
Deletion
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
luo_17_ASD/ADHD/DD_discovery_cases
Two patients with de novo 16q23.2-q23.3 deletions involving the CMIP gene
2
Both cases were diagnosed with ASD and ADHD (case 2 was additionally diagnosed with anxiety and pragmatic language disorder) and presented with developmental delay and significant gastrointestinal issues.
Range, 15-16 yrs.
Male
1590000
2
0
2
mahjani_21_ASD_discovery_cases
Study participants in the PAGES cohort, a large ongoing population-based cohort study in Sweden that started in 2012 with the overall aim to identify possible genetic and environmental risk factors for ASD.
996
Cases diagnosed with ASD according to ICD-9 and ICD-10 criteria.
Average age at diagnosis, 8.2 yrs.
70% Male
1510660
1
0
1
Controls
No Control Data Available
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
luo_17_ASD/ADHD/DD_discovery_cases
N/A
Solid phase hybridization
Illumina Human Q610, Illumina 850K BeadChip
CNV Workshop, Illumina GenomeStudio
FISH
mahjani_21_ASD_discovery_cases
Sweden
WES
Infinium OmniExpress Exome
PennCNV
NA
None
Controls
No Control Data Available
Cases
Patient ID
Author, Year
Age
Gender
Primary Diagnosis
Clinical Profile
Cognitive Profile
CNV Start
CNV End
CNV Size
Genome Build
Type Method
Validation
luo_17_ASD/ADHD/DD_discovery_cases-case1
16 yrs.
M
ASD and ADHD
Diagnosis of ASD and ADHD at 5 years of age. Birth and neonatal history: born at 33.5 weeks gestation to a 32-year-old G2P1; birth weight 85th %ile, birth length >99th %ile (50th %ile for 42 weeks corrected gestational age); congenital hip dislocation noted at birth; no other neonatal complications. Developmental milestones: normal gross motor development; mildly delayed language acquisition (began speaking at 14 months). Language and communication evaluation: persistent difficulties in communication and language development. Motor and musculoskeletal evaluation: thin body habitus; hypotonia. Behavioral/psychiatric evaluation: ASD, ADHD; atypical movements. Epilepsy/seizures: two seizure-like episodes. EEG: normal. Brain imaging: small pineal cyst on brain MRI. Auditory evaluation: impaired auditory processing. Additional medical history: failure to thrive, significant gastrointestinal issues (pancreatic insufficiency, antral web, slow gastric motility requiring G-tube feedings for 7 years starting from 3 years of age), twice daily diarrhea; episode of ileus at 16 years of age; persistent vomiting; gastroesophageal reflux disease; renal calcinosis (no current renal issues). Dysmorphic features: none reported. Growth parameters: height 55th %ile, weight 15th %ile, head circumference 50th %ile. Family history: family history significant for paternal second degree relatives with Graves disease and bipolar disorder; no family history of ASD or similar medical issues.
IQ testing at age of 13 years indicated a verbal IQ of 78 with a performance IQ of 55; case was at a second grade math level and a third grade reading level at the age of 15 years.
81399465
81916173
516709
GRCh38
Deletion
Yes
luo_17_ASD/ADHD/DD_discovery_cases-case2
15 yrs.
M
ASD and ADHD
Diagnosis of ASD at 4 years; case also diagnosed with anxiety, ADHD, and pragmatic language disorder. Birth and neonatal history: pregnancy conceived with use of Clomid, HCG trigger shot, and progesterone supplements; ultrasounds and karyotype by amniocentesis were normal; born at 36 weeks gestation to a 41-year-old G3P0 with two prior miscarriages; birth weight 80th %ile, birth length >99th %ile (50th %ile for 44 weeks gestational age); possible seizure resulted in brain MRI at 5 days of age showing perventricular leukomalacia along the frontal horns that resolved over time; significant issues with feeding, reflux, and projectile vomiting at 3 months, resulting in the need for nasogastric tube feedings for 9 months. Developmental milestones: sitting at 8 months, walking at 22 months. Language and communication evaluation: pragmatic language disorder. Motor and musculoskeletal evaluation: mild scoliosis, thin habitus, long fingers, long toes. Behavioral/psychiatric evaluation: ASD, ADHD, anxiety; standard score on Social Responsivenes Scale Growth of 86 at the age of 12 years; significant preoccupations; self-stimulatory behaviors; aggressive behavior. Epilepsy/seizures: possible seizure at 5 days of age. Brain imaging: brain MRI at 5 days of age showed perventricular leukomalacia along the frontal horns that resolved over time. Visual evaluation: myopia. Additional medical history: case underwent intensive feeding therapy at age of 2.5 years and gradually started to eat solid foods; vomiting improved at 5 years of age; poor food intake throughout childhood; constipation and gastroesophageal reflux requiring treatment with omeprazole and polyethylene glycol. Dysmorphic features: microretrognathia, relative prominence of the maxilla, hooded eyelids, prominent nose. Growth parameters: height 96th %ile, weight 27th %ile, head circumference 75th %ile; extremely low BMI (16.04 kg/m2; Z=-3.36) likely due to poor food intake.
Case was at a third grade reading level and a fourth grade math level at the age of 12 years.
80093429
81683275
1589847
GRCh38
Deletion
mahjani_21_ASD_discovery_cases-case220
NA
F
ASD
Diagnosis of ASD according to ICD-9 and ICD-10 criteria.
80450913
81961572
1510660
GRCh38
Deletion
No
Controls
No Control Data Available
Cases
Patient ID
Validation Description
Primary Disorder Inheritence
Inheritence
Family Profile
Disease Segregation
Gene Content
Altered Gene Expression
luo_17_ASD/ADHD/DD_discovery_cases-case1
FISH
De novo
Likely segregated
PPIAP51,MIR7854,MIR6504,CMIP,PLCG2
luo_17_ASD/ADHD/DD_discovery_cases-case2
De novo
Likely segregated
LINC01227,ATMIN,RNU6-1191P,MIR4720,PPIAP51,MIR7854,MIR6504,DYNLRB2,CENPN,C16orf46,GCSH,GAN,ARLNC1,CMC2,PKD1L2,BCO1,CMIP,CDYL2
mahjani_21_ASD_discovery_cases-case220
Unknown
BCO1,CMC2,CENPN,DYNLRB2,CMIP,CDYL2,PKD1L2,C16orf46,GCSH,PPIAP51,MIR4720,ARLNC1,PLCG2,LINC01227,DYNLRB2-AS1,MIR6504,MIR7854,RNU6-1191P,CENPN-AS1,GAN,ATMIN
Controls
No Control Data Available
No Animal Model Data Available