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

Nat Genet. 2008 Mar;40(3):322-8. doi: 10.1038/ng.93. Epub 2008 Feb 17.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chromosome Breakage
  • Chromosomes, Human, Pair 15*
  • Female
  • Gene Deletion*
  • Gene Frequency
  • Humans
  • Inheritance Patterns
  • Intellectual Disability / genetics*
  • Male
  • Pedigree
  • Receptors, Nicotinic / genetics
  • Seizures / genetics*
  • Syndrome
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Chrna7 protein, human
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor

Associated data

  • GEO/GSE10189