斑驳病3例基因变异检测及基因型与表型分析

doi:10.35541/cjd.20220380

中华皮肤科杂志 ›› 2024, Vol. 57 ›› Issue (1): 50-53.doi: 10.35541/cjd.20220380

斑驳病3例基因变异检测及基因型与表型分析

段紫钰¹ 段晓君² 薛晨红¹ 张守民¹ 李振鲁¹ 李建国¹ 王建波¹

¹河南省人民医院郑州大学人民医院河南大学人民医院皮肤科，郑州 450003；²河南省生殖健康科学技术研究院河南生殖妇产医院，郑州 450008

收稿日期:2022-05-27 修回日期:2023-08-21 发布日期:2024-01-05
通讯作者: 王建波；李建国 E-mail:wangjianbo1020@zzu.edu.cn; drljg006@163.com
基金资助:
河南省自然科学基金（202300410386）

Genetic variation analysis in three cases of piebaldism and analysis of the genotype-phenotype relationship

Duan Ziyu¹, Duan Xiaojun², Xue Chenhong¹, Zhang Shoumin¹, Li Zhenlu¹, Li Jianguo¹, Wang Jianbo¹

¹Department of Dermatology, Henan Provincial People′s Hospital, Zhengzhou University People′s Hospital, Henan University People′s Hospital, Zhengzhou 450003, China; ²Reproductive Obstetrics and Gynecology Hospital, Henan Institute of Reproductive Health Science and Technology, Zhengzhou 450008, China

Received:2022-05-27 Revised:2023-08-21 Published:2024-01-05
Contact: Wang Jianbo; Li Jianguo E-mail:wangjianbo1020@zzu.edu.cn; drljg006@163.com
Supported by:
Natural Science Foundation of Henan Province（202300410386）

摘要/Abstract

摘要： 【摘要】目的确定3例斑驳病患者的致病基因变异位点，探讨斑驳病基因型与表型的关系。方法 2019年1月至2021年12月于河南省人民医院皮肤科收集3例斑驳病患者及其父母临床资料，采集他们和100例无亲缘关系的健康对照外周血标本，提取全血DNA。应用全外显子测序技术筛选患者基因变异位点，Sanger测序验证。通过致病性分析软件评估变异位点的有害性。结果例1 男，23岁，额部和胸腹部白斑23年，父母未患病；例2男，1岁5个月，额部和腹部白斑1年，父母未患病；例3男，6岁，额部和四肢白斑6年，父母未患病。3例患者分别存在KIT基因14号外显子错义变异c.2033T>C（p.L678P）、18号外显子剪接位点变异c.2485-1G>C和16号外显子杂合错义变异c.2346C>G（p.F782L），而患者父母及100例健康对照均未发现上述3处变异。3个变异均为新致病变异位点，且均为有害致病变异位点。结论本研究在3例斑驳病患者中检测到3个新致病变异位点，即KIT基因c.2033T>C（p.L678P）、c.2485-1G>C和c.2346C>G（p.F782L）。进一步验证了该病严重程度与KIT基因变异的类型及位置密切相关。

关键词: 花斑, DNA突变分析, 基因型, 表型, 色素沉着不足, 斑驳病, KIT基因

Abstract: 【Abstract】 Objective To identify pathogenic genes in 3 cases of piebaldism, and to explore the genotype-phenotype relationships in piebaldism. Methods Clinical data were collected from 3 patients with piebaldism and their parents at the Department of Dermatology, Henan Provincial People′s Hospital from January 2019 to December 2021. Peripheral blood samples were obtained from them and 100 unrelated healthy controls, and DNA was extracted. Whole-exome sequencing technology was used to screen genetic variation sites, and then Sanger sequencing was performed for verification. The deleteriousness of genetic variants was evaluated by using pathogenicity analysis software tools. Results Case 1: a 23-year-old male patient presented with white patches on the forehead, chest, and abdomen for 23 years, and his parents had no similar symptoms; case 2: a 1-year- and 5-month-old male infant presented with white patches on the forehead and abdomen for 1 year, and his parents had no similar symptoms; case 3: a 6-year-old male child presented with white patches on the forehead and limbs for 6 years, and his parents had no similar clinical manifestations. Genetic testing showed that a missense mutation c.2033T>C （p.L678P） in exon 14 of the KIT gene, a splice site mutation c.2485-1G>C in exon 18 of the KIT gene, and a heterozygous missense mutation c.2346C>G （p.F782L） in exon 16 of the KIT gene were identified in the case 1, 2, 3 respectively, but no above mutations were identified in the patients′ parents or 100 unrelated healthy controls. The 3 genetic variants were all novel pathogenic mutations, and all were deleterious mutations. Conclusions Three novel pathogenic mutations in the KIT gene were identified in the 3 cases of piebaldism, namely c.2033T＞C （p.L678P）, c.2485-1G>C, and c.2346C>G （p.F782L）. It was further verified that the severity of piebaldism was closely related to the type and location of KIT gene mutations.

Key words: Piebaldism, DNA mutational analysis, Genotype, Phenotype, Hypopigmentation, Piebaldism, KIT gene

段紫钰段晓君王建波薛晨红张守民李建国李振鲁. 斑驳病3例基因变异检测及基因型与表型分析[J]. 中华皮肤科杂志, 2024,57(1):50-53. doi:10.35541/cjd.20220380

Duan Ziyu, Duan Xiaojun, Xue Chenhong, Zhang Shoumin, Li Zhenlu, Li Jianguo, Wang Jianbo. Genetic variation analysis in three cases of piebaldism and analysis of the genotype-phenotype relationship[J]. Chinese Journal of Dermatology, 2024, 57(1): 50-53.doi:10.35541/cjd.20220380

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斑驳病3例基因变异检测及基因型与表型分析

Genetic variation analysis in three cases of piebaldism and analysis of the genotype-phenotype relationship

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