1. ¹NE London Regional Cytogenetics Laboratory, Great Ormond Street Hospital NHS Trust, London, UK
2. ²NE Thames Regional Clinical Genetics Service, Institute of Child Health, London, UK
3. ³Cedar House, St Michael's Centre for Primary Care, Middlesex, UK
4. ⁴Paediatric Department, Chase Farm Hospital, Enfield, Middlesex, UK
5. ⁵National Genetics Reference Laboratory (Wessex), Salisbury NHS Foundation Trust, Salisbury, Wiltshire, UK
6. ⁶Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, Wiltshire, UK
7. ⁷Human Genetics Division, Southampton University School of Medicine, Southampton General Hospital, Southampton, UK

Correspondence: M Glancy, North East London Regional Cytogenetics Laboratory, Great Ormond Street Hospital NHS Trust, 2nd Floor, Institute of Neurology, Queen Square House, Queen Square, London, WC1N 3BG, UK. Tel: +44 207 829 8870; Fax: +44 207 813 8578; E-mail: glancm@gosh.nhs.uk

Received 28 August 2007; Revised 24 April 2008; Accepted 20 June 2008; Published online 20 August 2008.

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.