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

• DOI: 10.1038/ng.93
• Publication Date: 2008-02-17T19:38:06Z
• Authors: Andrew J Sharp; Heather C Mefford; Kelly Li; Carl Baker; Cindy Skinner; Roger E Stevenson; Richard J Schroer; Francesca Novara; Manuela De Gregori; Roberto Ciccone; Adam Broomer; Iris Casuga; Yu Wang; Chunlin Xiao; Catalin Barbacioru; Giorgio Gimelli; Bernardo Dalla Be...; Claudia Torniero; Roberto Giorda; Regina Regan; Victoria Murday; Sahar Mansour; Marco Fichera; Lucia Castiglia; Pinella Failla; Mario Ventura; Zhaoshi Jiang; Gregory M Cooper; Samantha J L Knight; Corrado Romano; Orsetta Zuffardi; Caifu Chen; Charles E Schwartz; Evan E Eichler
• Keywords: Male; Adolescent; alpha7 Nicotinic Acetylcholine Receptor; "EPILESSIA"; Inheritance Patterns; 610; Receptors, Nicotinic; Chromosome; Nicotinic; "DELEZIONI CRIPTICHE"; 03 medical and health sciences; Gene Frequency; Seizures; Intellectual Disability; 616; Humans; genetics; "NUOVE SINDROMI"; Preschool; Child; Chromosomes, Human, Pair 15; 0303 health sciences; Pair 15; Chromosome Breakage; Syndrome; Seizure; Pedigree; Child, Preschool; Female; Gene Deletion; Human; Receptor

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 approximately 0.3% (6/2,082 tested), a prevalence comparable to that of Williams, Angelman and Prader-Willi syndromes.