Nature Genetics
- 38, 1032 - 1037 (2006)
Published online: 13 August 2006; | doi:10.1038/ng1858
Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disabilityCharles Shaw-Smith1, 8, Alan M Pittman2, 8, Lionel Willatt3, 8, Howard Martin4, Lisa Rickman1, Susan Gribble5, Rebecca Curley5, Sally Cumming4, Carolyn Dunn3, Dimitrios Kalaitzopoulos5, Keith Porter5, Elena Prigmore5, Ana C V Krepischi-Santos6, Monica C Varela7, Celia P Koiffmann7, Andrew J Lees2, Carla Rosenberg6, Helen V Firth1, Rohan de Silva2 & Nigel P Carter51
University of Cambridge Department of Medical Genetics, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. 2
Reta Lila Weston Institute of Neurological Studies, University College London, 1 Wakefield Street, London, WC1N 1PJ, UK. 3
Regional Cytogenetics Laboratory, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. 4
Regional Molecular Genetics Laboratory, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. 5
The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. 6
Department of Genetics and Evolutionary Biology, University of São Paolo, PO Box 11461, 05422-970 São Paolo, Brazil. 7
Human Genome Research Centre, University of São Paolo, 05508-090 São Paolo, Brazil. 8
These authors contributed equally to this work.
Correspondence should be addressed to Charles Shaw-Smith css@sanger.ac.uk Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features1,
2,
3,
4. Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the deletions occurred as de novo events in each individual and were between 500 kb and 650 kb in size. A recently described 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes5 encompasses the deletion. We show that, in each trio, the parent of origin of the deleted chromosome 17 carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic architecture with well-described low-copy repeats (LCRs)5,
6. The orientation of LCRs flanking the deleted segment in inversion heterozygotes is likely to facilitate the generation of this microdeletion by means of non-allelic homologous recombination.
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