4q27-q28.1CNV Type: Deletion
Largest CNV size: 5680000 bp
Statistics Box:
Number of Reports: 2
Number of Reports: 2
Summary Information
A 5.68 Kb deletion within this region was found to segregate with a variety of neurodevelopmental and neuropsychiatric disorders (developmental delay/intellectual disability, ASD, and ADHD) in a three-generation pedigree (Hickey et al., 2013).
Additional Locus Information
References
Major Reports
Title
Author, Year
Report Class
CNV Type
Multigeneration family with short stature, developmental delay, and dysmorphic features due to 4q27-q28.1 microdeletion.
Deletion
Minor Reports
Title
Author, Year
Report Class
CNV Type
Performance of case-control rare copy number variation annotation in classification of autism.
Duplication
Cases
Cohort ID
Author, Year
Descripton
Cohort Size
Diagnosis
Age
Gender
CNV Size
Deletion
Duplication
Total CNV's
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
533188
0
1
1
hickey_13_DD/ID_discovery_cases
Affected members of a three generation pedigree shown to have a 4q27-q28.1 microdeletion
6
All six cases with developmental delay/intellectual disability, short stature, and facial dysmorphism; one case also diagnosed with ASD, ADHD, ODD, and mood disorder.
Range, 7-57 yrs.
50% Male
5680000
6
0
6
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
Cases
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
engchuan_15_ASD_discovery_cases
Caucasian
Solid phase hybridization
Illumina 1M
None
hickey_13_DD/ID_discovery_cases
Caucasian
aCGH, FISH
NimbleGen 135K
FISH
Controls
Cohort ID
Geographical Ancestry
Discovery Method
Platform
Algorithm
Software
Validation Method
engchuan_15_ASD_discovery_controls
Caucasian
Solid phase hybridization
Illumina 1M
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
engchuan_15_ASD_discovery_cases-case4290_1
N/A
N/A
ASD
Diagnosis of ASD based on Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R)
122778127
123311315
533189
GRCh38
Duplication
No
hickey_13_DD/ID_discovery_cases-caseI.2
57 yrs.
F
Developmental delay/intellectual disability
Clinical history: eye muscle surgery at age of 4 years, hypothyroidism, diagnosed with type 2 diabetes mellitus at age of 40. Growth parameters: height 4 ft. 7 in. Family history: sister with intellectual disability and short stature (case I.3; not tested); affected daugher (hickey_13_DD/ID_discovery_cases-caseII.2) and four affected grandchildren (hickey_13_DD/ID_discovery_cases-caseIII.1, hickey_13_DD/ID_discovery_cases-caseIII.2, hickey_13_DD/ID_discovery_cases-caseIII.3, & hickey_13_DD/ID_discovery_cases-caseIII.9) all carry familial 4q27.1-q28 microdeletion; affected son with short stature and learning disability (not tested, but obligate carrier of microdeletion); two affected grandchildren (cases III.8 and III.10) negative for 4q27.1-q28 microdeletion.
Self-described slow learner, completed 10th grade but did not graduate from high school
121615480
127293842
5678363
GRCh38
Deletion
No
hickey_13_DD/ID_discovery_cases-caseII.2
33 yrs.
F
Developmental delay/intellectual disability
Birth/neonatal history: born at 36 weeks gestation, spent 6 weeks in NICU postnatally for feeding problems. Developmental milestones: mild development delays during childhood. Clinical history: underlying fibrous dysplasia of bone discovered after case fractured arm as a teenager (three subsequent surgeries on that arm); history of migraine headaches since age of 21 years. Dysmorphic features: prominent forehead with large hemangioma, ocular hypertelorism with downslanting palpebral fissures. Growth parameters: height -3.2 SD (short stature). Family history: three affected offspring (hickey_13_DD/ID_discovery_cases-caseIII.1, hickey_13_DD/ID_discovery_cases-caseIII.2, & hickey_13_DD/ID_discovery_cases-caseIII.3), affected mother (hickey_13_DD/ID_discovery_cases-caseI.2), and affected nephew (hickey_13_DD/ID_discovery_cases-caseIII.9) all carry familial 4q27-q28.1 microdeletion); brother with short stature and learning disability (case II.6, not tested but obligate carrier of microdeletion); two affected nephews (case III.8 & caseIII.10) negative for microdeletion.
Intellectual disability; attended special education classes and graduated high school
121615480
127293842
5678363
GRCh38
Deletion
No
hickey_13_DD/ID_discovery_cases-caseIII.1
12 yrs.
M
Developmental delay/intellectual disability
Birth/neonatal history: born at 35 weeks gestation weighing 5 lbs.; presented to Genetics at 4 months (imperforate anus). Developmental milestones: did not walking until 17 months but was saying several words. Epilepsy/seizures: tonic-clonic seizures at 9 months (prescribed carbamazepine), one additional seizure at age of 8 years. Brain imaging: normal brain MRI in infancy. Clinical history: colostomy take-down with bowel re-anastomosis; diagnosed with megacolon by abdominal MRI at age of 3.5 years, unable to have bowel movement without daily senokot and polyethylene glycol; atrial septal defect closure via catheterization procedure; strabismus. Dysmorphic features: broad forehead, ocular hypertelorism, epicanthal folds, midface hypoplasia. Family history: two affected siblings (hickey_13_DD/ID_discovery_cases-caseIII.2 & hickey_13_DD/ID_discovery_cases-caseIII.3), affected mother (hickey_13_DD/ID_discovery_cases-caseII.2), affected maternal grandmother (hickey_13_DD/ID_discovery_cases-caseI.2), and affected maternal cousin (hickey_13_DD/ID_discovery_cases-caseIII.9) all carry familial 4q27-q28.1 microdeletion; two maternal cousins with intellectual disability and short stature (III.8) and delayed speech and seizures (III.10) negative for familial deletion.
Attending regular kindergarten at age of 6 years
121615480
127293842
5678363
GRCh38
Deletion
Yes
hickey_13_DD/ID_discovery_cases-caseIII.2
9 yrs.
M
Developmental delay/intellectual disability
Birth/neonatal history: born at full-term weighing 5 lbs. 10 ozs.; evaluated by Genetics at 2 months; developed gastroesophageal reflux disease (GERD) and constipation; hospitalized at age of 14 months to Gastroenterology service for one week due to failure to thrive, upper endoscopy with biposy unremarkable. Developmental milestones: 5-10 words at age of 20 months; found to have developmental articulation delay at age of 5.5 years. Language and communication evaluation: begun to receive speech and language therapy and school intervention services. Motor and musculoskeletal evaluation: back-arching from GERD; casting for 6 weeks for toe-walking without change in gait; lumbar spine MRI showed subtle bright T1 signal intensity within filum terminale compatible with filar lipoma with no evident secondary changes of tethering. Behavioral/psychiatric evaluation: self-abusive behaviors, aggressive behaviors to others. Clinical history: gastrointestinal symptoms had resolved by age of 20 months; hearing within normal limits; normal echocardiogram; infrequent urinary voiding and some episodes of fecal incontinence at age of 6 years; L5 laminotomy with filum terminale resection performed for urinary and bowel symptoms. Dysmorphic features: prominent forehead, ocular hypertelorism, ptosis, short upturned nose, single transverse palmar crease. Growth parameters: height -2 SD. Family history: two affected siblings (hickey_13_DD/ID_discovery_cases-caseIII.1 & hickey_13_DD/ID_discovery_cases-caseIII.3), affected mother (hickey_13_DD/ID_discovery_cases-caseII.2), affected maternal grandmother (hickey_13_DD/ID_discovery_cases-caseI.2), and affected maternal cousin (hickey_13_DD/ID_discovery_cases-caseIII.9) all carry familial 4q27-q28.1 microdeletion; two maternal cousins with intellectual disability and short stature (III.8) and delayed speech and seizures (III.10) negative for familial deletion.
121615480
127293842
5678363
GRCh38
Deletion
No
hickey_13_DD/ID_discovery_cases-caseIII.3
7 yrs.
F
Developmental delay/intellectual disability
Birth/neonatal history: born at full-term and weighed 6 lbs. 8 ozs.; ongoing problems with GERD (prescribed slow flow nipple, ranitidine, and metoclopramide); length at 5 months <3rd %ile. Developmental milestones: walked at 15 months (toe-walked). Clinical history: began seeing gastroenterologist at age of 3 years for ongoing emesis; normal upper GI series; allergist found allergies to milk, soy, and possibly eggs; trialed on omeprazole and lansoprazole with minimal effect; failed hearing test and had myringotomy tubes placed; normal echocardiogram. Dysmorphic features: ocular hypertelorism, midface hypoplasia, ptosis, stellate pattern to iris, and relative macrocephaly. Growth parameters: height -1.3 SD. Family history: two affected siblings (hickey_13_DD/ID_discovery_cases-caseIII.1 & hickey_13_DD/ID_discovery_cases-caseIII.2), affected mother (hickey_13_DD/ID_discovery_cases-caseII.2), affected maternal grandmother (hickey_13_DD/ID_discovery_cases-caseI.2), and affected maternal cousin (hickey_13_DD/ID_discovery_cases-caseIII.9) all carry familial 4q27-q28.1 microdeletion; two maternal cousins with intellectual disability and short stature (III.8) and delayed speech and seizures (III.10) negative for familial deletion.
121615480
127293842
5678363
GRCh38
Deletion
No
hickey_13_DD/ID_discovery_cases-caseIII.9
9 yrs.
M
Developmental delay/intellectual disability, ASD, and ADHD
Initially evaluated by clinical geneticist at 6 years for short stature and failure to thrive. Birth/neonatal history: born at full-term weighing 6 lbs. 13 ozs.; concerns about gastroesophageal reflux (GERD) and weight at 11 months (subsequently treated with Pediasure). Developmental milestones: speech onset at 2 years of age. Epilepsy/seizures: one febrile seizure. Behavioral/psychiatric evaluation: diagnosed with autism spectrum disorder, ADHD, oppositional defiant disorder (ODD), anxiety, and mood disorder; feeding refusal behaviors. Clinical history: history of unilateral conductive hearing loss (treated with myringotomy tubes), wore glasses for hyperopia with astigmatism, unremarkable echocardiogram; normal renal ultrasound, growth hormone therapy prescribed but discontinued due to patient refusal. Growth parameters: height -2 SD. Family history: father with short stature and learning disability (not tested, but obligate carrier for 4q27-q28.1 microdeletion); two affected siblings (case III.8 with intellectual disability and short stature, case III.10 with delayed speech and seizures) negative for 4q27-q28.1 microdeletion; three affected paternal cousins (hickey_13_DD/ID_discovery_cases-caseIII.1, hickey_13_DD/ID_discovery_cases-caseIII.2, & hickey_13_DD/ID_discovery_cases-caseIII.3), affected paternal aunt (hickey_13_DD/ID_discovery_cases-caseII.2), and affected paternal grandmother (hickey_13_DD/ID_discovery_cases-caseI.2) all carry familial 4q27-q28.1 microdeletion.
121615480
127293842
5678363
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
engchuan_15_ASD_discovery_cases-case4290_1
Unknown
FGF2,NUDT6,SPATA5
hickey_13_DD/ID_discovery_cases-caseI.2
Unknown
Multi-generational
Incomplete segregation (6/8 affected family members that have been tested were positive for 4q27-q28.1 microdeletion)
TMEM155,CCNA2,RN7SL335P,CETN4P,BBS12,SPRY1,RPL21P50,PPIAP76,TECRP2,MIR2054,TMEM248P1,LINC02379,RBM48P1,ANXA5,EXOSC9,BBS7,IL2,IL21,FGF2,NUDT6,LINC02435,ANKRD50,NUP58P1,PP12613,TRPC3,KIAA1109,ADAD1,SPATA5,LINC02516,FAT4,IL21-AS1,LINC01091
hickey_13_DD/ID_discovery_cases-caseII.2
Maternal
Multi-generational
Incomplete segregation (6/8 affected family members that have been tested were positive for 4q27-q28.1 microdeletion)
TMEM155,CCNA2,RN7SL335P,CETN4P,BBS12,SPRY1,RPL21P50,PPIAP76,TECRP2,MIR2054,TMEM248P1,LINC02379,RBM48P1,ANXA5,EXOSC9,BBS7,IL2,IL21,FGF2,NUDT6,LINC02435,ANKRD50,NUP58P1,PP12613,TRPC3,KIAA1109,ADAD1,SPATA5,LINC02516,FAT4,IL21-AS1,LINC01091
hickey_13_DD/ID_discovery_cases-caseIII.1
FISH
Maternal
Multi-generational
Incomplete segregation (6/8 affected family members that have been tested were positive for 4q27-q28.1 microdeletion)
TMEM155,CCNA2,RN7SL335P,CETN4P,BBS12,SPRY1,RPL21P50,PPIAP76,TECRP2,MIR2054,TMEM248P1,LINC02379,RBM48P1,ANXA5,EXOSC9,BBS7,IL2,IL21,FGF2,NUDT6,LINC02435,ANKRD50,NUP58P1,PP12613,TRPC3,KIAA1109,ADAD1,SPATA5,LINC02516,FAT4,IL21-AS1,LINC01091
hickey_13_DD/ID_discovery_cases-caseIII.2
Maternal
Multi-generational
Incomplete segregation (6/8 affected family members that have been tested were positive for 4q27-q28.1 microdeletion)
TMEM155,CCNA2,RN7SL335P,CETN4P,BBS12,SPRY1,RPL21P50,PPIAP76,TECRP2,MIR2054,TMEM248P1,LINC02379,RBM48P1,ANXA5,EXOSC9,BBS7,IL2,IL21,FGF2,NUDT6,LINC02435,ANKRD50,NUP58P1,PP12613,TRPC3,KIAA1109,ADAD1,SPATA5,LINC02516,FAT4,IL21-AS1,LINC01091
hickey_13_DD/ID_discovery_cases-caseIII.3
Maternal
Multi-generational
Incomplete segregation (6/8 affected family members that have been tested were positive for 4q27-q28.1 microdeletion)
TMEM155,CCNA2,RN7SL335P,CETN4P,BBS12,SPRY1,RPL21P50,PPIAP76,TECRP2,MIR2054,TMEM248P1,LINC02379,RBM48P1,ANXA5,EXOSC9,BBS7,IL2,IL21,FGF2,NUDT6,LINC02435,ANKRD50,NUP58P1,PP12613,TRPC3,KIAA1109,ADAD1,SPATA5,LINC02516,FAT4,IL21-AS1,LINC01091
hickey_13_DD/ID_discovery_cases-caseIII.9
Unknown (likely paternal)
Multi-generational
Incomplete segregation (6/8 affected family members that have been tested were positive for 4q27-q28.1 microdeletion)
TMEM155,CCNA2,RN7SL335P,CETN4P,BBS12,SPRY1,RPL21P50,PPIAP76,TECRP2,MIR2054,TMEM248P1,LINC02379,RBM48P1,ANXA5,EXOSC9,BBS7,IL2,IL21,FGF2,NUDT6,LINC02435,ANKRD50,NUP58P1,PP12613,TRPC3,KIAA1109,ADAD1,SPATA5,LINC02516,FAT4,IL21-AS1,LINC01091
Controls
No Control Data Available
No Animal Model Data Available