Piebaldism with café-au-lait macules resulting from a novel mutation of KIT gene in a three-generation Chinese family.

Abstract

BACKGROUND:

Piebaldism is a rare, autosomal dominant, and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SLUG genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder.

METHODS:

In this paper, we report a case of piebaldism with café-au-lait macules resulting from a novel mutation of KIT gene c.1982C > T (p.Thr661Ile) in a three-generation Chinese family. The whole-exome sequencing, mitochondrial gene 3000X, and bioinformatics tools were used to identify the mutation in this new-found pedigree. In addition, we searched the databases of "Punmed, Chinese National Knowledge Infrastructure, CMJD, WANFANG MED ONLINE", reviewed 88 cases of piebaldism caused by KIT gene mutation, and summarized the relationship between clinical phenotype and genotype of piebaldism through logistic regression and other statistical methods.

RESULTS:

The proband and her affected mother carried a heterozygous c.1982C > T missense mutation (p.Thr661Ile) on KIT gene. Bioinformatics analysis hinted that it had potential pathogenicity. The data showed that piebaldism patients with cafè-au-lait macules had KIT mutations almost located in the intracellular tyrosine kinase domain and were mostly related to the severe clinical phenotype of piebaldism.

CONCLUSION:

The new heterozygous c.1982C > T missense mutation on KIT caused piebaldism with café-au-lait macules in this Chinese family. This study provides a new reference index for clinicians to judge the severity of clinical phenotypes of piebaldism, broadens the understanding of the correlation between clinical phenotypes and genotypes of piebaldism, and provides reference of genetic counseling and prenatal diagnosis for affected families.

• Authors: Xiaorong Li, Xiaojing Xing, Xiaoqiang Liang, Cuihao Song, Jie Yang, Dan Ren, Yong Zhou
• Journal: Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) (Skin Res Technol) Vol. 29 Issue 6 Pg. e13352 (Jun 2023) ISSN: 1600-0846 [Electronic] England
• PMID: 37357653 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.

Chemical References

• Proto-Oncogene Proteins c-kit

Topics

• Humans
• Female
• Piebaldism (genetics)
• Proto-Oncogene Proteins c-kit (genetics)
• Cafe-au-Lait Spots (diagnosis, genetics)
• Mutation (genetics)
• Pigmentation Disorders