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.