Department of Dermatology, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
Department of Dermatology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Skin Res Technol. 2023 Jun;29(6):e13352. doi: 10.1111/srt.13352.
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.
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.
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.
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.
斑驳病是一种罕见的常染色体显性遗传性先天性色素障碍性疾病，其特征为皮肤稳定脱色和白色额发。KIT 或 SLUG 基因突变导致斑驳病。大多数斑驳病患者有该病家族史。
本文报道了一个三代表亲中国家族中由 KIT 基因 c.1982C>T（p.Thr661Ile）新突变引起的伴有咖啡牛奶斑的斑驳病病例。使用全外显子组测序、线粒体基因 3000X 和生物信息学工具在新发现的家系中鉴定突变。此外，我们在“Punmed、中国知网、CMJD、万方医学在线”数据库中检索，综述了 88 例 KIT 基因突变致斑驳病的病例，通过逻辑回归等统计学方法总结斑驳病基因型与临床表型的关系。
先证者及其受累母亲均携带 KIT 基因杂合 c.1982C>T 错义突变（p.Thr661Ile）。生物信息学分析提示其具有潜在致病性。数据表明，伴有咖啡牛奶斑的斑驳病患者 KIT 基因突变几乎位于细胞内酪氨酸激酶结构域，且与斑驳病的严重临床表型关系密切。
KIT 上的新杂合 c.1982C>T 错义突变导致该中国家系发生伴有咖啡牛奶斑的斑驳病。本研究为临床医生判断斑驳病临床表型严重程度提供了新的参考指标，拓宽了对斑驳病临床表型与基因型相关性的认识，为受累家系提供了遗传咨询和产前诊断的参考。
