两个原发性限局性皮肤淀粉样变家系的致病突变鉴定  

Identification of pathogenic mutations in two Chinese families affected with primary localized cutaneous amyloidosis

作　　者：茅彬 姚煦 王铮[1] 赵秀丽[1] 

机构地区：[1]中国医学科学院基础医学研究所-北京协和医学院基础学院医学遗传学系,北京100005 [2]中国医学科学院皮肤病研究所过敏与风湿免疫科,南京210042

出　　处：《中华医学遗传学杂志》2018年第1期9-13,共5页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划（2016YFC0905100）

摘　　要：目的对两个中国人原发性限局性皮肤淀粉样变家系进行致病基因的突变鉴定。方法在取得知情同意后，采集家系成员的外周血，使用酚-氯仿法提取基因组DNA；应用PCR扩增两家系先证者OSMR基因的全部17个外显子及外显子／内含子衔接区，通过Sanger测序鉴定候选致病突变；通过PCR-限制性片段长度多态性分析以及高分辨熔解曲线分析进行致病突变的家系验证。结果家系1中6例患者均携带OSMR基因第10外显子c．1538G〉A错义突变，家系2中4例患者均携带OSMR基因第14外显子C-2081C〉T错义突变；两个家系中所有正常个体及健康对照均未携带上述突变。结论在两个原发性限局性皮肤淀粉样变家系中发现了OSMR基因内的两个错义突变（C．1538G〉A和C．2081C〉T）。该结果与既往的报道一致，再次证明了这些突变的致病性。Objective To identify potential mutations in two Chinese families affected with primary localized cutaneous amyloidosis. Methods Peripheral blood samples of the family were collected with informed consent. Genomic DNA was extracted with a phenol-chloroform method. All of the 17 exons and their flanking splicing sites of the OSMR gene were amplified with PCR and subjected to Sanger sequencing. Suspected mutations were verified with PCR-restriction fragment length polymorphism and high-resolution melting assays. Results A missense mutation （c. 1538G〉A） was found in exon 10 of the OSMR gene in all of the six patients from family 1. A missense mutation （c. 2081C〉T） was found in exon 14 of the OSMR gene in all of the four patients from family 2. The same mutations were not found among the healthy controls. Conclusion Two missense mutations （c. 1538G〉A and c. 2081C〉T） were detected in the OSMR gene in two Chinese families affected with primary localized cutaneous amyloidosis. Our findings have further confirmed the pathogenicity of such mutations.

关 键 词：原发性限局性皮肤淀粉样变 OSMR基因 突变鉴定 高分辨熔解曲线 

分 类 号：R758.6[医药卫生—皮肤病学与性病学]