PDF(Pubmed)
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：Piebaldism是一种罕见的，常染色体显性,和先天性色素性疾病的特征是稳定的皮肤色素脱失和白色的前额。KIT或SLUG基因的突变导致piebaldism。大多数患有piebalism的人都有该疾病的家族史。
方法：在本文中，我们报告了一例由KIT基因c.19822C>T的新突变引起的Café-au-lait黄斑斑病（p。Thr661Ile）在一个三代中国家庭中。全外显子组测序,线粒体基因3000X,和生物信息学工具被用来鉴定这个新发现的谱系中的突变。此外,我们搜索了“Punmed”的数据库，中国国家知识基础设施，CMJD,旺方在线留言，“回顾了88例KIT基因突变引起的piebalism，并通过logistic回归等统计方法总结了临床表型与基因型的关系。
结果：先证者及其受影响的母亲携带杂合c.1982C>T错义突变（p。Thr661Ile)对KIT基因。生物信息学分析提示其具有潜在的致病性。数据显示，患有cfé-au-lait黄斑的piebaldism患者的KIT突变几乎位于细胞内酪氨酸激酶结构域，并且主要与piebaldism的严重临床表型有关。
结论：KIT上的新杂合c.1982C>T错义突变在该中国家族中引起了带café-au-lait斑疹的piebaldism。本研究为临床医师判断中医临床表型的严重程度提供了新的参考指标,拓宽了对piebaldism临床表型和基因型之间相关性的理解，为患病家庭提供遗传咨询和产前诊断参考。
方法：在本文中，我们报告了一例由KIT基因c.19822C>T的新突变引起的Café-au-lait黄斑斑病（p。Thr661Ile）在一个三代中国家庭中。全外显子组测序,线粒体基因3000X,和生物信息学工具被用来鉴定这个新发现的谱系中的突变。此外,我们搜索了“Punmed”的数据库，中国国家知识基础设施，CMJD,旺方在线留言，“回顾了88例KIT基因突变引起的piebalism，并通过logistic回归等统计方法总结了临床表型与基因型的关系。
结果：先证者及其受影响的母亲携带杂合c.1982C>T错义突变（p。Thr661Ile)对KIT基因。生物信息学分析提示其具有潜在的致病性。数据显示，患有cfé-au-lait黄斑的piebaldism患者的KIT突变几乎位于细胞内酪氨酸激酶结构域，并且主要与piebaldism的严重临床表型有关。
结论：KIT上的新杂合c.1982C>T错义突变在该中国家族中引起了带café-au-lait斑疹的piebaldism。本研究为临床医师判断中医临床表型的严重程度提供了新的参考指标,拓宽了对piebaldism临床表型和基因型之间相关性的理解，为患病家庭提供遗传咨询和产前诊断参考。
