2. Academic Validation
  3. Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems

Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems

  • Am J Hum Genet. 2005 Jul;77(1):120-6. doi: 10.1086/431244.
Alice S Brooks 1,  Aida M Bertoli-Avella,  Grzegorz M Burzynski,  Guido J Breedveld,  Jan Osinga,  Ludolf G Boven,  Jane A Hurst,  Grazia M S Mancini,  Maarten H Lequin,  Rene F de Coo,  Ivana Matera,  Esther de Graaff,  Carel Meijers,  Patrick J Willems,  Dick Tibboel,  Ben A Oostra,  Robert M W Hofstra
Affiliations

Affiliation

  • 1 Department of Clinical Genetics, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands.
PMID: 15883926 DOI: 10.1086/431244
Abstract

We identified, by homozygosity mapping, a novel locus on 10q21.3-q22.1 for Goldberg-Shprintzen syndrome (GOSHS) in a consanguineous Moroccan family. Phenotypic features of GOSHS in this inbred family included microcephaly and mental retardation, which are both central nervous system defects, as well as Hirschsprung disease, an enteric nervous system defect. Furthermore, since bilateral generalized polymicogyria was diagnosed in all patients in this family, this feature might also be considered a key feature of the syndrome. We demonstrate that homozygous nonsense mutations in KIAA1279 at 10q22.1, encoding a protein with two tetratrico peptide repeats, underlie this syndromic form of Hirschsprung disease and generalized polymicrogyria, establishing the importance of KIAA1279 in both enteric and central nervous system development.

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