一个假性软骨发育不良家系临床及软骨低聚物基质蛋白基因突变分析  

Clinical features and gene mutation analysis of cartilage oligomeric matrix protein in a family with pseudoachondroplasia

作　　者：郑瑞芝[1] 周炳喜[1] 王剑 汪艳芳[1] 赵志刚[1] 马跃华[1] 刘宏霞[1] 虎子颍[1] 张俐[1] 

机构地区：[1]河南省人民医院内分泌代谢科,郑州450003 [2]上海儿童医学中心儿科转化医学研究所

出　　处：《中华内分泌代谢杂志》2016年第1期47-51,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：河南省卫生厅医学学术技术带头人出国培训计划项目（201201086）;河南省科技厅基础研究计划项目（142300410071）;河南省卫生厅科技攻关计划项目（201303123）

摘　　要：目的对一家系三代2例假性软骨发育不良（PSACH）患者及其家系成员进行软骨低聚物基质蛋白（COMP）基因突变分析，以明确基因型与I临床表型的关系。方法收集先证者及其家系成员临床资料及外周全血标本，采用PCR—DNA直接测序技术对患者及其家系成员及50个无血缘关系的个体进行COMP基因19个外显子及侧翼序列突变分析。结果先证者为女孩，6岁，具有短肢侏儒、步态蹒跚、双膝内翻畸形、长骨干骺端增宽等临床及影像学表现；先证者父亲，33岁，临床表现与患者类似，具有短肢侏儒、双膝内翻畸形，10岁时曾行双下肢矫正手术。序列分析显示，家系中先证者及其父亲均存在COMP基因外显子13上c．1417_1419delGAC缺失突变，余家系成员及50个对照均无异常。结论COMP基因c．1417—1419GAC缺失突变可能导致了此PSACH家系的临床表现。Objective To investigate cartilage oligomeric matrix protein（COMP） gene mutation in a three- generation pedigree with two cases of pseudoachondroplasia, and to definitize genotype-phenotype correlation. Methods The clinical data and peripheral blood were collected from the patients with pseudoacbondroplasia and their family members. All the 19 exons and their flanking sequences of COMP gene in two patients and three unaffected family numbers and 50 unrelated individuals were analyzed by PCR amplification and direct sequencing. Results The proband, a 6-year-old girl presented with typical clinical features of pseudoachondroplasia, including disproportionate short limb dwarfism, staggering gait, double genu varus deformity, and wider clinical and imaging long bone metaphysis. The 33-year-old father showed a similar manifestation including disproportionate short limb dwarfism and double genu varus deformity, and was performed correcting operation on lower limbs for double genu varus at the age of 10 years. DNA sequencing analysis of the COMP gene revealed a del mutation （ c. 1417_ 1419delGAC ） in exon 13 in two patients with pseudoachondroplasia, but not in the other unaffected members from the pedrgree and 50 control subjects. Conclusion A del mutation c. 1417_1419delGAC of COMP gene may contribute to the disease in the pedigree.

关 键 词：假性软骨发育不良 软骨低聚物基质蛋白 基因突变 

分 类 号：R681.1[医药卫生—骨科学]