Copy number changes of the microcephalin 1 gene (MCPH1) in patients with autism spectrum disorders.
Autism spectrum disorder (ASD) represents a set of neurodevelopmental disorders with a strong genetic aetiology. Chromosomal rearrangements have been detected in 5-10% of the patients with ASD, and recent applications of array comparative genomic hybridisation (aCGH) are identifying further candidate regions and genes. In this study, we present four patients who implicate microcephalin 1 (MCPH1) in band 8p23.1 as an ASD susceptibility gene. Patient 1 was a girl with a syndromic form of autistic disorder satisfying the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS) and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Oligonucleotide aCGH (oaCGH) showed that she had a classic inv dup del(8)(qter-> p23.1::p23.1-> p21.2) containing at least three candidate genes; MCPH1 and DLGAP2 within the 6.9-Mb terminal deletion and NEF3 within the concomitant 14.1-Mb duplication. Three further patients with MCPH1 copy number changes were found using single-nucleotide polymorphism (SNP) array analysis in a cohort of 54 families with ASD patients. Our results show that ASD can be a component of the classical inv dup del(8) phenotype and identify changes in copy number of MCPH1 as a susceptibility factor for ASD in the distal short arm of chromosome 8.
Ozgen
H M
HM
Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands. h.m.ozgen@umcutrecht.nl
van Daalen
E
E
Bolton
P F
PF
Maloney
V K
VK
Huang
S
S
Cresswell
L
L
van den Boogaard
M J
MJ
Eleveld
M J
MJ
van 't Slot
R
R
Hochstenbach
R
R
Beemer
F A
FA
Barrow
M
M
Barber
J C K
JC
Poot
M
M
D018797:Cell Cycle Proteins; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D020732:Cytogenetic Analysis; D003598:Cytoskeletal Proteins; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins