Human piebaldism: six novel mutations of the proto-oncogene KIT.
Human piebaldism is a rare autosomal dominant disorder that comprises congenital patchy depigmentation of the scalp, forehead, trunk and limbs. It is caused by mutations in the cell-surface receptor tyrosine kinase gene (KIT, also c-kit). We screened three families and three isolated cases of piebaldism from different countries for mutations in the KIT gene using automated sequencing methods. We report six novel KIT point mutations: three missense (C788R, W835R, P869S) at highly conserved amino acid sites; one nonsense (Q347X) that results in termination of translation of the KIT gene in exon 6; and two splice site nucleotide substitutions (IVS13+2T>G, IVS17-1G>A) that are predicted to impair normal splicing. These mutations were not detected in over 100 normal individuals and are likely to be the cause of piebaldism in our subjects.
Medical Genetics Unit, St George's Hospital Medical School, London, United Kingdom. psyrris@sghms.ac.uk
Petros
P
Syrris
Kirsten
K
Heathcote
Romeo
R
Carrozzo
Koen
K
Devriendt
Nursel
N
Elçioglu
Christine
C
Garrett
Meriel
M
McEntagart
Nicholas D
ND
Carter
D000328:Adult; D017398:Alternative Splicing / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D016116:Piebaldism / Q000235:genetics*; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit