Copy number changes of the microcephalin 1 gene (MCPH1) in patients with autism spectrum disorders

Clin Genet. 2009 Oct;76(4):348-56. doi: 10.1111/j.1399-0004.2009.01254.x.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins
  • Child
  • Child Development Disorders, Pervasive / genetics*
  • Child Development Disorders, Pervasive / pathology
  • Child, Preschool
  • Chromosomes, Human, Pair 8 / genetics*
  • Cytogenetic Analysis
  • Cytoskeletal Proteins
  • DNA Copy Number Variations / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Nerve Tissue Proteins / genetics*
  • Phenotype*
  • Polymorphism, Single Nucleotide


  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • MCPH1 protein, human
  • Nerve Tissue Proteins