一个中国近端指（趾）骨间关节黏连家系NOG基因新突变鉴定  

Identification of a novel NOG mutation in a Chinese family with proximal symphalangism

作　　者：王蓉蓉[1] 韩士瑞 周宗伟[3] 白晓[1] 张颖[4] 张学[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,北京100005 [2]中国医科大学基础医学院细胞生物学系 [3]温州医科大学附属第二医院骨科 [4]天津医科大学总医院产科

出　　处：《国际遗传学杂志》2017年第1期1-5,共5页International Journal of Genetics

基　　金：基金项目：国家自然科学基金项目（81230015）;国家重点研发计划项目（2016YFC1000504）;生物医药与生命科学创新培育研究（Z151100003915078）

摘　　要：目的检测一个中国近端指（趾）骨问关节黏连家系的致病基因突变。方法收集该家系患者和家系成员的临床资料，采集外周血提取基因组DNA。运用聚合酶链式反应和Sanger测序法筛查先证者的NOG和GDF5基因。确定突变位点后，在家系成员中进行共分离分析并在200名正常对照中筛查该突变。结果该家系患者中存在NOG基因c．502T〉C错义突变，该突变导致其编码蛋白Noggin第168位氨基酸由苯丙氨酸变为亮氨酸（P．F168L）。在家系正常成员和200名正常对照中未检测到相同突变。该突变在dbSNP、ExAC等数据库中未见报道。在GDF5基因上未发现可疑突变。结论NOG基因c．502T〉C错义突变是该家系发病的原因。Objective To identify the pathogenic mutation underlying proximal symphalangism in a Chinese family. Methods A five-generation family showing an autosomal dominant transmission of proximal symphalangism was examined. To screen the pathogenic mutation in NOG and GDFS, we PCR- amplified the exons and exon-intron boundaries of the two genes and sequenced them directly after purifica- tion. Results We found a novel heterozygous missense mutation, c. 502 T 〉 C, in NOG. This mutation led to a substitution of phenylalanine by leucine at amino acid residue 168 of Noggin （ p. F 168 L ）. The mutation co-segregated with the limb phenotype of all the family members but was not present in public databases （ dbSNP and ExAC ） or 200 control individuals. Conclusion The c. 502 T 〉 C mutation in NOG is a novel pathogenic mutation for the proximal symphalangism phenotype in this family.

关 键 词：近端指(趾)骨间关节黏连 NOG基因 基因突变 

分 类 号：R681.1[医药卫生—骨科学]