Guangdong Medical College, College of Dermatology, Anhui Medical University, Guangzhou, China.
Guangdong Provincial Dermatology Hospital, Guangzhou, China.
Am J Med Genet A. 2020 Jun;182(6):1321-1328. doi: 10.1002/ajmg.a.61576. Epub 2020 Mar 27.
Piebaldism is a rare, autosomal dominant and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SNAI2 genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. Herein, we report a 5-month-old Chinese girl with severe piebaldism but no family history thereof. She has white forelock and large patches of depigmentation in the jaw, central anterior trunk, perineum and extremities. We performed whole-exome and Sanger sequencing and identified a de novo KIT mutation (NM_000222.2: c.2657G>A, p.Gly886Val) in exon 18 of KIT in the proband. Currently, this mutation is located in the most extreme C-terminal of the tyrosine kinase domain 2 of the KIT gene amongst all reported mutations and causes a severe clinical phenotype. We further reviewed literature on piebaldism and summarized 79 KIT gene mutations that lead to this disease. Our study may expand knowledge on the genotype-phenotype correlation in piebaldism and serve as a reference for genetic counseling and prenatal diagnosis of affected families.
斑驳病是一种罕见的常染色体显性遗传和先天性色素障碍性疾病，其特征为皮肤稳定的脱色和白头。KIT 或 SNAI2 基因突变导致斑驳病。大多数斑驳病患者都有该病的家族史。在此，我们报告一例 5 月龄中国女婴，患有严重的斑驳病，但无家族史。她有白头和下颌、中央前躯干、会阴和四肢的大块脱色。我们进行了全外显子组和 Sanger 测序，在先证者的 KIT 基因外显子 18 中发现了一个 KIT 突变（NM_000222.2：c.2657G>A，p.Gly886Val）。目前，该突变位于所有报道的突变中 KIT 基因酪氨酸激酶域 2 的最极端 C 末端，导致严重的临床表型。我们进一步复习了斑驳病的文献，并总结了导致该病的 79 个 KIT 基因突变。我们的研究可能会扩展对斑驳病基因型-表型相关性的认识，并为受影响家庭的遗传咨询和产前诊断提供参考。
