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.