Haploinsufficiency of CELF4 at 18q12.2 is associated with developmental and behavioral disorders, seizures, eye manifestations, and obesity

Eur J Hum Genet. 2012 Dec;20(12):1315-9. doi: 10.1038/ejhg.2012.92. Epub 2012 May 23.

Abstract

Only 20 patients with deletions of 18q12.2 have been reported in the literature and the associated phenotype includes borderline intellectual disability, behavioral problems, seizures, obesity, and eye manifestations. Here, we report a male patient with a de novo translocation involving chromosomes 12 and 18, with borderline IQ, developmental and behavioral disorders, myopia, obesity, and febrile seizures in childhood. We characterized the rearrangement with Affymetrix SNP 6.0 Array analysis and next-generation mate pair sequencing and found truncation of CELF4 at 18q12.2. This second report of a patient with a neurodevelopmental phenotype and a translocation involving CELF4 supports that CELF4 is responsible for the phenotype associated with deletion of 18q12.2. Our study illustrates the utility of high-resolution genome-wide techniques in identifying neurodevelopmental and neurobehavioral genes, and it adds to the growing evidence, including a transgenic mouse model, that CELF4 is important for human brain development.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CELF Proteins
  • Chromosomes, Human, Pair 12 / genetics
  • Chromosomes, Human, Pair 18 / genetics
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics*
  • Genetic Association Studies
  • Haploinsufficiency
  • Humans
  • Male
  • Myopia / diagnosis
  • Myopia / genetics*
  • Obesity / diagnosis
  • Obesity / genetics*
  • RNA-Binding Proteins / genetics*
  • Seizures / diagnosis
  • Seizures / genetics*
  • Syndrome
  • Translocation, Genetic

Substances

  • CELF Proteins
  • CELF4 protein, human
  • RNA-Binding Proteins