遗传性多发性外生骨疣基因突变研究  

Identification of mutations in the human EXT1 and EXT2 genes

作　　者：宋国清[1,2,3] 周江南[1,2,3] 夏家辉[1,2,3] 邓汉湘 徐磊[1,2,3] 黄蕾 阮庆国[1,2,3] 

机构地区：[1]湖南医科大学附属湘雅医院 [2]医学遗传学国家重点实验室 [3]湖南医科大学附属第三医院骨科

出　　处：《中华医学遗传学杂志》1999年第4期208-210,共3页Chinese Journal of Medical Genetics

摘　　要：目的进一步阐明遗传性多发性外生骨疣（ｈｅｒｅｄｉｔａｒｙｍｕｌｔｉｐｌｅｅｘｏｓｔｏｓｅｓ，ＥＸＴ）的发病机理，并为最终防治本病提供依据。方法采用聚合酶链反应－单链构象多态性分析，在３０个ＥＸＴ家系中进行ＥＸＴ１基因和ＥＸＴ２基因全部外显子突变检测，并对发现的致病突变进行ＤＮＡ测序分析。结果在２个家系中发现了致病突变，并经ＤＮＡ序列分析证实，一个系ＥＸＴ１基因ｅｘｏｎ６区域单个碱基（Ｔ）丢失；另一个系ＥＸＴ２基因ｅｘｏｎ２区域４个碱基（ｔｇｔ）丢失，前者系国内首次报道，后者系尚未见报道的新突变，这两种突变均系移码突变。结论ＥＸＴ１基因或ＥＸＴ２基因突变，可导致ＥＸＴ，本研究结果可直接应用于ＥＸＴ的遗传咨询和产前基因诊断。Objective To investigate further the genetic basis of hereditary multiple exostoses (EXT) and provide useful information for gene diagnosis of the disease. Methods Polymerase chain reactionsingle strand conformation polymorphism(PCRSSCP) was used to examine the entire coding regions of EXT1 gene on chromosome 8 and EXT2 gene on chromosome 11 for mutation in thirty EXT families. Mutations were further identified by sequencing. Results Two frameshift mutations were identified in two unrelated EXT families. One was the deletion of one base(T) in exon 6 of the EXT1 gene, and the other was the deletion of four bases (tgtt) in exon 2 of the EXT2 gene. Both of the mutations resulted in a frameshift and premature termination of translation. Conclusion EXT is a genetically heterogeneous bone disorder caused by the mutation of EXT tumor suppressor gene. These results could be directly applied in the genetic counselling and prenatal genetic diagnosis of EXT.

关 键 词：遗传性多发性 外生骨疣 EXT 基因突变 骨骼疾病 

分 类 号：R681.02[医药卫生—骨科学]