遗传性多发性骨软骨瘤的基因突变筛查及基因型与表型关系的研究  

Gene mutation screening and the genotype-phenotype correlation of hereditary multiple exostoses

作　　者：王剑[1] 李玉婵[2] 李怀远[1] 郁婷婷[1] 傅启华[1] 

机构地区：[1]上海交通大学医学院附属上海儿童医学中心检验科,200127 [2]上海交通大学医学院附属上海儿童医学中心骨科,200127

出　　处：《中华检验医学杂志》2010年第10期926-930,共5页Chinese Journal of Laboratory Medicine

基　　金：上海市卫生局科研基金资助项目（2008195）

摘　　要：目的建立HME的基因突变筛查方法,并探讨其基因型与临床表型的关系.方法根据临床诊断将15例HME先证者分为轻度（M）和重度（Ⅰ S、ⅡS、ⅢS）4型,运用PCR扩增产物直接测序法对先证者及其家系成员进行EXT1和EXT2基因序列分析,筛查其EXT1和EX72基因突变,并分析基因型与临床表型之间的关系.结果 15例HME先证者中有9例为EXT1基因突变,6例为EXT2基因突变,其中EXT1基因I8＋2T＞G、c.1182deIG、c.1108G＞T（p.E370X）、c.335de1A、c.361C＞T（p.Q121X）和c.18791881delCAC为国际上新发现的基因突变位点.EXT1基因突变患者临床表型分别为M型2例（22.2%,2/9）、Ⅰ S型2例、ⅡS型4例和ⅢS型1例,而EXT2基因突变患者M型有5例（83.3%,5/6）,另1例为ⅡS型.结论本研究建立了HME准确、简便的EXT1和EXT2基因突变筛查方法,6个EXT1基因突变I8＋2T＞G、c.1182delG、c.1108G＞T（p.E370X）、c.335delA、c.361C＞T（p.Q121X）和c.1879_1881delCAC为国际首次报道,EXT1基因突变患者相比EXT2基因突变患者临床表型要更严重.Objective To establish the method of gene mutation screening for HME and investigate the relationship between genotype and clinical phenotype in HME patients. Methods Fifteen cases of HME probands were divided into the following four subgroups： mild （M） and severe （ Ⅰ S, Ⅱ S, Ⅲ S） according to the clinical diagnosis. DNA samples were obtained from the probands and family members. All of the EXT1 and EXT2 gene exons and their boundary sequences were amplified by PCR, and sequenced by directsequencing. Then the relationship between the genotypes and clinical phenotype was analyzed. Results Among the fifteen cases of HME probands, nine harbored EXT1 gene mutation, while the other 6 were positive for EXT2 gene mutation. Moreover, six novel mutations in EXT1 gene, including I8 ＋ 2T 〉 G, c. 1182delG,c. 1108G 〉T（p. E370X） ,c. 335delA,c. 361C 〉T（p. Q121X） and c. 1879_1881delCAC were identified. In 9 patients with EXT1 gene mutation, 2 （22. 2% ） were M-type, 2 （22. 2% ） were Ⅰ S -type, 4 （44. 4% ）were Ⅱ S-type,and 1 （ 11.1% ） was ⅢS-type. Whereas, 5 cases （83.3%） were M-type and only one case was Ⅱ S-type（ 16. 7% ） in 6 patients with EXT2 gene mutation. Conclusions An accurate and simple gene diagnostic method for HME was established. Six novel EXT1 gene mutations, including I8 ＋ 2T 〉 G,c. 1182delG, c. 1108G 〉T（p. E370X）, c. 335delA, c. 361C 〉T（p. Q121X）and c. 1879_1881delCAC were identified as well. The clinical phenotype of the patients with EXT1 gene mutation was more severe compared to those with EXT2 gene mutations.

关 键 词：外生骨疣 多发性遗传性 N-乙酰氨基葡糖转移酶类 基因 肿瘤抑制 突变 基因型 表型 

分 类 号：R686[医药卫生—骨科学]