Homozygous nonsense mutations in KIAA1279 are associated with malformations of the central and enteric nervous systems.
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.
Brooks
Alice S
AS
Department of Clinical Genetics, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands.
Bertoli-Avella
Aida M
AM
Burzynski
Grzegorz M
GM
Breedveld
Guido J
GJ
Osinga
Jan
J
Boven
Ludolf G
LG
Hurst
Jane A
JA
Mancini
Grazia M S
GM
Lequin
Maarten H
MH
de Coo
Rene F
RF
Matera
Ivana
I
de Graaff
Esther
E
Meijers
Carel
C
Willems
Patrick J
PJ
Tibboel
Dick
D
Oostra
Ben A
BA
Hofstra
Robert M W
RM
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
D018389:Codon, Nonsense; C503132:KIFBP protein, human; D009419:Nerve Tissue Proteins