一个低血磷性佝偻病家系的基因突变检测及产前诊断  

Mutational analysis and prenatal diagnosis in a family affected with hypophosphatemic rickets

作　　者：栾兆棠 李焕铮 胡林 陈冲 徐雪琴 项延包 唐少华 Luan Zhaotang Li Huanzheng Hu Lin Chen Chong Xu Xueqin Xiang Yanbao Tang Shaohua(School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou , Zhejiang 325035, China Central Laboratory, the Central Hospital of Wenzhou, Wenzhou, Zhejiang 325000, China （Li HZ, ChenC, Xu XQ, Xiang YB)

机构地区：[1]浙江省温州医科大学检验医学院、生命科学学院,325035 [2]浙江省温州市中心医院中心实验室,325000

出　　处：《中华医学遗传学杂志》2017年第5期633-636,共4页Chinese Journal of Medical Genetics

基　　金：浙江省人口计生委项目（JSW2012-B003）;温州市科技计划项目（Y20150092）;浙江省自然科学基金（LQ1GH200001）

摘　　要：目的通过对1个低血磷性佝偻病家系的临床表征及基因突变分析，揭示其遗传发病机制，为家系的遗传咨询及产前诊断提供依据。方法对该家系先证者进行全外显子组测序，结合临床表型及遗传方式分析，选定X染色体上PHEX基因的一个移码突变C．2058—2059insAGTT（p．L686{s）为可疑致病突变。对先证者及其他家系成员进行Sanger测序验证。孕18周时抽取先证者羊水，进行产前诊断。结果全外显子测序结果显示先证者PHEX基因存在C．2058—2059insAGTT（p．L686fs）杂合突变，经Sanger测序验证结果显示先证者及其母亲均携带PHEX基因C．2058—2059insAGTT（p．L686fs）杂合突变，正常家系成员均未检测到该突变；产前诊断结果显示，胎儿与先证者基因型一致。结论PHEX基因C．2058—2059insAGTT突变为该低血磷性佝偻病家系的致病原因，为家系的遗传咨询及产前诊断提供了依据。Objective To explore the,clinical characteristics and genetic mutation in a family affected with hypophosphatemic rickets. Methods Whole exome sequencing （WES） was used to screen potential mutations in genomic DNA extracted from peripheral venous blood sample from the proband. Suspected mutation was confirmed with Sanger sequencing. Amniotic fluid was sampled from the proband for prenatal diagnosis. Potential maternal contamination was excluded by analysis of short tandem repeat （STR） markers. Results WES has identified a heterozygous c. 2058 2059insAGTT （p. L686fs） mutation of the PHEX gene in the proband, which was confirmed by Sanger sequencing in other affected individuals from the family. The mutation was detected in the amniotic fluid sample from the fetus but not among healthy members from the family. Conclusion Identification of the PHEX mutation by WES has facilitated genetic counseling and orenatal diagnosis for the family affected with hypoohosohatemic rickets.

关 键 词：低磷性佝偻病 PHEX基因 基因突变 产前诊断 

分 类 号：R440[医药卫生—诊断学] R596[医药卫生—临床医学]