title: Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems.
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.
authors.affiliation: Department of Clinical Genetics, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Brooks
authors.forename: Aida M
authors.initials: AM
authors.lastname: Bertoli-Avella
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Burzynski
authors.forename: Guido J
authors.initials: GJ
authors.lastname: Breedveld
authors.forename: Jan
authors.initials: J
authors.lastname: Osinga
authors.forename: Ludolf G
authors.initials: LG
authors.lastname: Boven
authors.forename: Jane A
authors.initials: JA
authors.lastname: Hurst
authors.forename: Grazia M S
authors.initials: GM
authors.lastname: Mancini
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Lequin
authors.forename: Rene F
authors.initials: RF
authors.lastname: de Coo
authors.forename: Ivana
authors.initials: I
authors.lastname: Matera
authors.forename: Esther
authors.initials: E
authors.lastname: de Graaff
authors.forename: Carel
authors.initials: C
authors.lastname: Meijers
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Willems
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Robert M W
authors.initials: RM
authors.lastname: Hofstra
mesh_terms: D000015:Abnormalities, Multiple; D001483:Base Sequence; D002879:Chromosomes, Human, Pair 10; D018389:Codon, Nonsense; D003241:Consanguinity; D017615:Enteric Nervous System / Q000002:abnormalities*; D005260:Female; D006627:Hirschsprung Disease / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D009419:Nerve Tissue Proteins; D009421:Nervous System Malformations / Q000235:genetics*; D010375:Pedigree; D013577:Syndrome
chemical_list: D018389:Codon, Nonsense; C503132:KIFBP protein, human; D009419:Nerve Tissue Proteins