摘要目的 研究家族遗传性骨软骨瘤病(hereditary multiple exostoses,HME)的致病基因及产前诊断.方法 应用连锁分析方法对一个HME家系EXT1、EXT2和EXT3基因进行分析.致病基因定位后,用PCR-测序法进行了突变分析.结果 在该家系中EXT2基因第6外显子发生1个新的无义突变(c.1006C>T),该突变导致第336位编码谷氨酰胺的密码子CAA变为终止密码子TAA(Gln336X).根据上述结果配合遗传咨询进行了产前诊断,结果显示胎儿正常.结论 在家族遗传性骨软骨瘤家系中发现一新的EXT2基因突变,并应用于产前诊断.

abstractsObjective Hereditary multiple exostoses (HME) is an autosomai dominant disorder characterized by formation of benign cartilage-capped tumors (exostoses), typically located at the juxtaepiphyseal regions of long bones. It is genetically heterogeneous with at least three chromosomal loci: EXT1 on 8q24. 1, EXT2 on 11p11, and EXT3 on 19p. EXT1 and EXT2 have been cloned and are responsible for over 80% of cases. A Chinese family with HME has been analyzed in the present study. Methods Linkage analysis was firstly performed to determine which of the three EXT genes could be the candidate gene, then mutation screening by PCR and direct sequencing was carried out. Results A novel nonsense mutation (c. 1006C>T) in exon 6 of EXT2, which converts the codon CAA (Gin) to the stop codon (TAA) (Gln336X), was identified. Next, prenatal diagnosis was performed and the pregnancy was determined to be normal. Conclusion A new EXT2 nonsense mutation was found in a Chinese family with hereditary multiple exostoses. The information was used for a case of prenatal diagnosis.