title: Lack of c-kit mutation in familial urticaria pigmentosa.
abstract: Somatic mutations within c-kit have been reported in individuals with mastocytoses, including urticaria pigmentosa (UP). We have identified three siblings with UP. We aimed to determine whether the c-kit proto-oncogene was playing a part in the aetiology of UP in these three siblings. Using seven microsatellite repeat markers spanning an 8-cM interval encompassing the c-kit gene we followed the transmission of the c-kit gene in this family. Furthermore, single-strand conformation polymorphism analysis was used to scan exon 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 proband. No mutations were found in exon 17 in either genomic DNA of all family 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 been 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 emphasizes genetic heterogeneity in UP. Future study to identify primary molecular determinants of UP should include affected sib-pair studies.
authors.affiliation: Department of Dermatology, St Helier Hospital, Carshalton, Surrey SM5 1AA, U.K.
authors.forename: J L
authors.initials: JL
authors.lastname: Rosbotham
authors.forename: N M
authors.initials: NM
authors.lastname: Malik
authors.forename: P
authors.initials: P
authors.lastname: Syrris
authors.forename: S
authors.initials: S
authors.lastname: Jeffery
authors.forename: A
authors.initials: A
authors.lastname: Bedlow
authors.forename: S
authors.initials: S
authors.lastname: Gharraie
authors.forename: V A
authors.initials: VA
authors.lastname: Murday
authors.forename: C A
authors.initials: CA
authors.lastname: Holden
authors.forename: N D
authors.initials: ND
authors.lastname: Carter
mesh_terms: D002675:Child, Preschool; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D014582:Urticaria Pigmentosa / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit