Lack of c-kit mutation in familial urticaria pigmentosa

Somatic mutations within c-kit have been reported in individuals with masto cytoses, including urticaria pigmentosa (UP), We have identified three sibl ings with UP, We aimed to determine whether the c-kit proto-oncogene was pl aying a part in the aetiology of UP in these three siblings. Using seven mi crosatellite repeat markers spanning an 8-cM internal encompassing the c-ki t gene we followed the transmission of the c-kit gene in this family, Furth ermore, single-strand conformation polymorphism analysis was used to scan e xon 17 of the c-kit gene for mutations in genomic DNA of all family members and somatic DNA extracted from skin of the eldest affected sibling, the pr oband, No mutations were found in exon 17 in either genomic DNA of all fami ly members or somatic DNA of the proband, Patients with UP have been shown to possess somatic mutations of the c-kit gene. However, this locus has bee n excluded as playing a part in the three siblings examined here in whom a second gene locus must be determining their UP, Therefore, this study empha sizes genetic heterogeneity in UP, Future study to identify primary molecul ar determinants of UP should include affected sib-pair studies.