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Novel mutations and deletions of the KIT (steel factor receptor) gene in human piebaldism
K Ezoe1, S A Holmes, L Ho
1Department of Medical Genetics, University of Wisconsin, Madison 53706.
Abstract:
Piebaldism is an autosomal dominant genetic disorder of pigmentation characterized by white patches of skin and hair. Melanocytes are lacking in these hypopigmented regions, the result of mutations of the KIT gene, which encodes the cell surface receptor for steel factor (SLF). We describe the analysis of 26 unrelated patients with piebaldism-like hypopigmentation--17 typical patients, 5 with atypical clinical features or family histories, and 4 with other disorders that involve white spotting. We identified novel pathologic mutations or deletions of the KIT gene in 10 (59%) of the typical patients, and in 2 (40%) of the atypical patients. Overall, we have identified pathologic KIT gene mutations in 21 (75%) of 28 unrelated patients with typical piebaldism we have studied. Of the patients without apparent KIT mutations, none have apparent abnormalities of the gene encoding SLF itself (MGF), and genetic linkage analyses in two of these families are suggestive of linkage of the piebald phenotype to KIT. Thus, most patients with typical piebaldism appear to have abnormalities of the KIT gene.
Insights
Most piebaldism cases are caused by mutations in the KIT gene, which affects skin and hair pigmentation. This genetic disorder results in white patches due to a lack of melanocytes.
Area of Science:
- Genetics
- Dermatology
- Molecular Biology
Background:
- Piebaldism is an autosomal dominant disorder causing white patches in skin and hair.
- It results from a lack of melanocytes in hypopigmented areas.
- Mutations in the KIT gene, encoding the steel factor receptor, are implicated.
Purpose of the Study:
- To analyze the KIT gene in patients with piebaldism-like hypopigmentation.
- To identify the genetic basis of the disorder in a cohort of patients.
- To determine the frequency of KIT gene mutations in typical and atypical cases.
Main Methods:
- Genetic analysis of 26 unrelated patients with piebaldism-like hypopigmentation.
- Categorization of patients into typical, atypical, and other white spotting disorders.
- Mutation screening and deletion analysis of the KIT gene.
Main Results:
- Novel KIT gene mutations/deletions identified in 59% of typical and 40% of atypical patients.
- Overall, 75% of typical piebaldism patients studied had pathogenic KIT mutations.
- No abnormalities found in the MGF gene (encoding SLF) in patients without KIT mutations.
Conclusions:
- Most patients with typical piebaldism exhibit abnormalities of the KIT gene.
- Genetic linkage suggests piebaldism phenotype is linked to KIT.
- KIT gene mutations are the primary cause of most piebaldism cases.