Skip to Main content Skip to Navigation
Journal articles

A family with autism and rare copy number variants disrupting the Duchenne/Becker muscular dystrophy gene DMD and TRPM3.

Abstract : Autism spectrum disorder is a genetically complex and clinically heterogeneous neurodevelopmental disorder. A recent study by the Autism Genome Project (AGP) used 1M single-nucleotide polymorphism arrays to show that rare genic copy number variants (CNVs), possibly acting in tandem, play a significant role in the genetic aetiology of this condition. In this study, we describe the phenotypic and genomic characterisation of a multiplex autism family from the AGP study that was found to harbour a duplication of exons 31-44 of the Duchenne/Becker muscular dystrophy gene DMD and also a rare deletion involving exons 1-9 of TRPM3. Further characterisation of these extremely rare CNVs was carried out using quantitative PCR, fluorescent in situ hybridisation, long-range PCR amplification and sequencing of junction fragments. The maternal chrX:32,097,213-32,321,945 tandem duplication and paternal chr9:72,480,413-73,064,196 deletion (NCBI build 36 coordinates) were transmitted to both affected boys, potentially signifying a multi-hit mechanism. The DMD reading frame rule predicts a Becker phenotype, characterised by later onset and milder symptoms. When last evaluated, neither child had developed signs of muscular dystrophy. These data are consistent with a degree of comorbidity between autism and muscular dystrophy and suggest that genomic background as well as the position of the mutation within the DMD gene may impact on the neurological correlates of Duchenne/Becker muscular dystrophy. Finally, communicating unexpected findings such as these back to families raises a number of ethical questions, which are discussed.
Document type :
Journal articles
Complete list of metadata
Contributor : Catalina Betancur <>
Submitted on : Tuesday, June 7, 2011 - 6:41:58 PM
Last modification on : Friday, May 28, 2021 - 11:52:09 AM
Long-term archiving on: : Friday, September 9, 2011 - 3:21:58 PM




Alistair Pagnamenta, Richard Holt, Mohammed Yusuf, Dalila Pinto, Kirsty Wing, et al.. A family with autism and rare copy number variants disrupting the Duchenne/Becker muscular dystrophy gene DMD and TRPM3.. Journal of Neurodevelopmental Disorders, BioMed Central, 2011, 3 (2), pp.124-31. ⟨10.1007/s11689-011-9076-5⟩. ⟨inserm-00598894⟩



Record views


Files downloads