[A novel KIT gene mutation results in piebaldism].

To detect gene mutation in proband and his mother from a family with piebaldism. Diagnosis of a patient with piebaldism was validated by pathology, ultrastructural examination and the typical clinical manifestation. PCR and DNA sequencing were carried out to detect gene mutation of a family with piebaldism. G1833A transition in the KIT gene was found in the proband of the family with piebaldism. This mutation resulted in V604I substitution in KIT gene. No mutation was found in 100 normal individuals and other family members. The mutation of V604I is the cause of clinical phenotype of the family with piebaldism.

Deng WP ，Lu C ，Zhu GX ，Lin QD ，Feng PY ... -  《-》

[A novel KIT gene mutation from a family with piebaldism in the southern part of China].

To detect the gene mutation of a family with piebaldism. Diagnosis of a patient with piebaldism was constructed by pathology, ultrastructural examination and typical clinical-phenotype. Detection of gene mutation was carried out by PCR and DNA sequencing. G 2528A substitution transition in the KIT gene was found in the proband of the family with piebaldism. This mutation resulted in S850N substitution in protein product of KIT gene. No mutation was found in 100 normal individuals and other family members. The mutation of S850N maybe one cause of clinical phenotype of the family with piebaldism.

Deng WP ，Huang YS ，Lu C ，Lan W ，Zhu GX ，Lin QD ，Feng PY ... -  《-》

A novel KIT mutation results in piebaldism with progressive depigmentation.

Piebaldism is an autosomal dominant disorder of melanocyte development characterized by white skin (leukoderma) and white hair (poliosis). In general, piebaldism has been distinguished from vitiligo by the presence of lesions from birth, the hyperpigmented macules of depigmented and normal skin, and the static course. We hypothesized that an 8-year-old girl and her mother who had unusual piebaldism of a progressive nature would have a novel mutation of the KIT gene, the gene that is altered in patients with piebaldism, or of the MITF (microphthalmia activating transcription factor) gene, which would be expected to cause type II Waardenburg syndrome, but is associated with a phenotype of progressive depigmentation in mice. Genomic DNA was extracted from the blood of affected and unaffected family members, and the KIT and MITF genes were sequenced. Genetic analysis of genomic DNA from both the mother and daughter with progressive piebaldism revealed a novel Val620Ala (1859T>C) mutation in the KIT gene, which was not detected in family members without progressive piebaldism or in 52 normal control individuals. This KIT mutation affects the intracellular tyrosine kinase domain and thus predicts a severe phenotype, as was the case in this family. Although other KIT mutations in the vicinity of codon 620 lead to the standard phenotype of static piebaldism, the Val620Ala mutation is novel and may result in a previously undescribed phenotype with melanocyte instability, leading to progressive loss of pigmentation as well as the progressive appearance of the hyperpigmented macules.

Richards KA ，Fukai K ，Oiso N ，Paller AS ... -  《JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY》

A novel KIT missense mutation in one Chinese family with piebaldism.

Piebaldism is an autosomal dominant disorder characterized by congenital leukoderma, mostly affecting forehead, abdomen and knee. Previous studies have revealed that piebaldism is caused by mutations of the KIT gene, which encodes the cell surface transmembrane tyrosine kinase receptor for KIT ligand. We reported here a Chinese Han family with piebaldism, and performed mutation detection of KIT gene by direct sequencing. A novel missense mutation C58G was identified in the patients, but not in the healthy individuals from the family and 100 unrelated controls. This study contributes to the database on KIT in piebaldism and enriches the knowledge about the genotype/phenotype correlation.

Yin XY ，Ren YQ ，Yang S ，Xu SX ，Zhou FS ，Du WH ，Lin D ，Wang PG ，Zhang SM ，Zhang XJ ... -  《-》

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.

Syrris P ，Heathcote K ，Carrozzo R ，Devriendt K ，Elçioglu N ，Garrett C ，McEntagart M ，Carter ND ... -  《-》