Abstract
Duplications of distal 8p with and without significant clinical phenotypes have been reported and are often associated with an unusual degree of structural complexity. Here, we present a duplication of 8p23.1–8p23.2 ascertained in a child with speech delay and a diagnosis of ICD-10 autism. The same duplication was found in his mother who had epilepsy and learning problems. A combination of cytogenetic, FISH, microsatellite, MLPA and oaCGH analysis was used to show that the duplication extended over a minimum of 6.8 Mb between 3 539 893 and 10 323 426 bp. This interval contains 32 novel and 41 known genes, of which only microcephalin (MCPH1) is a plausible candidate gene for autism at present. The distal breakpoint of the duplicated region interrupts the CSMD1 gene in 8p23.2 and the medial breakpoint lies between the MSRA and RP1L1 genes in 8p23.1.
An interchromosomal insertion between a normal and polymorphically inverted chromosome 8 is proposed to explain the origin of this duplication. Further mapped imbalances of distal 8p are needed to determine whether the autistic component of the phenotype in this family results from the cumulative imbalance of many genes or dosage imbalance of an individual susceptibility gene.
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Acknowledgements
We are grateful to the Sanger Centre for providing the Ensembl tiling path clones and to Dr Hiroaki Shizuya for kindly providing BAC 51D11. SH and VKM are supported as part of the National Genetics Reference Laboratory (Wessex) by the UK Department of Health Genetics, Embryology and Assisted Conception Unit. The image enhancement equipment used for this work was provided by the Welcome Trust and Trust Funds of Salisbury NHS Health Care Trust
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Glancy, M., Barnicoat, A., Vijeratnam, R. et al. Transmitted duplication of 8p23.1–8p23.2 associated with speech delay, autism and learning difficulties. Eur J Hum Genet 17, 37–43 (2009). https://doi.org/10.1038/ejhg.2008.133
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DOI: https://doi.org/10.1038/ejhg.2008.133
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