Letter abstract

Nature Genetics 40, 322 - 328 (2008)
Published online: 17 February 2008 | doi:10.1038/ng.93

A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures

Andrew J Sharp1,15, Heather C Mefford1, Kelly Li2, Carl Baker1, Cindy Skinner3, Roger E Stevenson3, Richard J Schroer3, Francesca Novara4, Manuela De Gregori4, Roberto Ciccone4, Adam Broomer2, Iris Casuga2, Yu Wang2, Chunlin Xiao2, Catalin Barbacioru2, Giorgio Gimelli5, Bernardo Dalla Bernardina6, Claudia Torniero6, Roberto Giorda7, Regina Regan8, Victoria Murday9, Sahar Mansour10, Marco Fichera11, Lucia Castiglia11, Pinella Failla11, Mario Ventura12, Zhaoshi Jiang1, Gregory M Cooper1, Samantha J L Knight8, Corrado Romano11, Orsetta Zuffardi4,13, Caifu Chen2, Charles E Schwartz3 & Evan E Eichler1,14


We report a recurrent microdeletion syndrome causing mental retardation, epilepsy and variable facial and digital dysmorphisms. We describe nine affected individuals, including six probands: two with de novo deletions, two who inherited the deletion from an affected parent and two with unknown inheritance. The proximal breakpoint of the largest deletion is contiguous with breakpoint 3 (BP3) of the Prader-Willi and Angelman syndrome region, extending 3.95 Mb distally to BP5. A smaller 1.5-Mb deletion has a proximal breakpoint within the larger deletion (BP4) and shares the same distal BP5. This recurrent 1.5-Mb deletion contains six genes, including a candidate gene for epilepsy (CHRNA7) that is probably responsible for the observed seizure phenotype. The BP4–BP5 region undergoes frequent inversion, suggesting a possible link between this inversion polymorphism and recurrent deletion. The frequency of these microdeletions in mental retardation cases is approx0.3% (6/2,082 tested), a prevalence comparable to that of Williams, Angelman and Prader-Willi syndromes.

  1. Department of Genome Sciences, University of Washington School of Medicine, 1705 NE Pacific St., Seattle, Washington 98195, USA.
  2. Assays/Arrays R&D, Applied Biosystems, Foster City, California 94404, USA.
  3. JC Self Research Institute, Greenwood Genetic Center, Greenwood, South Carolina 29646, USA.
  4. Biologia Generale e Genetica Medica, Università di Pavia, Pavia 27100, Italy.
  5. Istituto G. Gaslini, Genova 16147, Italy.
  6. Servizio Neuropsichiatria Infantile, Policlinico GB Rossi, Università di Verona, Verona 37134, Italy.
  7. IRCCS E. Medea, Bosisio Parini 23842, Italy.
  8. Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, The Wellcome Trust Centre for Human Genetics, Churchill Hospital, Oxford OX3 7BN, UK.
  9. Department of Medical Genetics, Duncan Guthrie Institute, Glasgow G3 8SJ, UK.
  10. SW Regional Genetics Service, St George's Hospital, London SW17 0RE, UK.
  11. IRCCS Associazione Oasi Maria Santissima, Troina 94018, Italy.
  12. Dipartimento di Genetica e Microbiologia, Universita' degli Studi di Bari, Bari 27100, Italy.
  13. Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy.
  14. Howard Hughes Medical Institute, 1705 NE Pacific St., Seattle, Washington 98195, USA.
  15. Present address: Department of Genetic Medicine and Development, University of Geneva Medical School, 1 rue Michel-Servet, 1211 Geneva, Switzerland.

Correspondence to: Evan E Eichler1,14 e-mail: eee@gs.washington.edu