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Copy number changes of the microcephalin 1 gene (MCPH1) in patients with autism spectrum disorders |
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| Authors: | HM Ozgen E van Daalen PF Bolton VK Maloney S Huang L Cresswell MJ van den Boogaard MJ Eleveld R van 't Slot R Hochstenbach FA Beemer M Barrow JCK Barber M Poot |
| Affiliation: | Department of Child and Adolescent Psychiatry;, and Rudolf Magnus Institute of Neuroscience, University Medical Centre, Utrecht, The Netherlands;, Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, London, UK;, National Genetics Reference Laboratory (Wessex), Salisbury Hospital NHS Trust, Salisbury, Wiltshire SP2 8BJ, UK;, Leicestershire Genetics Centre, Leicester Royal Infirmary, Leicester LE1 5WW, UK;, Department of Medical Genetics, University Medical Centre, Utrecht, The Netherlands;, Wessex Regional Genetics Laboratory, Salisbury Hospital NHS Trust, Salisbury, Wiltshire SP2 8BJ, UK;, and Human Genetics Division, Southampton University School of Medicine, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK |
| Abstract: | 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. |
| Keywords: | autism spectrum disorder copy number changes deletion duplication oligonucleotide array CGH SNP arrays microcephalin 1 |