Lack ofc-kitmutation 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.

C-kit Asp-816-Val Mutation Analysis in Patients with Mastocytosis

“…The Asp-816-Val mutation could not be demonstrated in familial urticaria pigmentosa. This is consistent with earlier publications, although we only studied 2 cases [6, 7]. The suggested absence of Asp-816-Val mutation in familial cases of mastocytosis must be further evaluated in such populations.…”

“…Mastocytosis in adults frequently is a persisting or progressive disorder, whereas in many children the disorder resolves with age [4, 5]. Although generally mastocytosis is a rare disorder, families have been described in which more than one member is affected [6]. In patients with mastocytosis, symptoms are primarily caused by the release of mast cell mediators, although they may also be due to local accumulation of mast cells.…”

“…Mutations in c-kit may lead to SCF-independent activation of the receptor, preventing proliferation and apoptosis of mast cells [7, 8]. In familial forms of mastocytosis, the Asp-816-Val mutation has never been demonstrated [6, 7]. …”

Pediatric Mastocytosis Is a Clonal Disease Associated with D816V and Other Activating c-KIT Mutations

“…The other two lacked c-KIT mutations. In contrast, Longley et al (1996) did not find exon 17 mutations in three cases of familial childhood mastocytosis, and, similarly, Rosbotham et al (1999) did not find exon 17 mutations in three siblings with familial urticaria pigmentosa. Furthermore, the four patients in this study with familial mastocytosis lacked the A 533 D germline mutation that was previously reported in a kindred with childhood-onset familial mastocytosis (Tang et al, 2004), as well as the D 419 and K 509 I mutations, which were originally identified in kindreds with a combination of familial GISTs and mastocytosis (Hartmann et al, 2005) and with familial mastocytosis (Zhang et al, 2006), respectively.…”

Mastocytosis: a rare case of anaphylaxis in paediatric age and literature review

“…6 Rosbotham et al estimated that there are two new cases per year in a population of 300,000 corresponding to an incidence of 0.000667 %. 7 Mastocytosis occurs equally in both sexes and as been described in different ethnic groups, although there are more reports in caucasians. 8 …”