多发性骨骺发育不良患者软骨寡聚物基质蛋白基因新突变

A novel mutation of cartilage oligomeric matrix protein gene underlies multiple epiphyseal dysplasia

目的对1例多发性骨骺发育不良女性患者的软骨寡聚物基质蛋白（cartilageoligomericmatrixprotein，COMP）基因进行突变分析，为遗传咨询和产前分子诊断提供指导。方法采集患者血样，提取基因组DNA，用外显子序列捕获＋第二代测序技术对COMP基因进行基因突变的检测并用聚合酶链反应结合Sanger法核苷酸序列测定进行突变位点验证。结果该患者COMP基因第9外显子存在C．956A〉T错义突变，其COMP基因第319位密码子由原来编码天冬氨酸的密码子GAC突变为编码缬氨酸的密码子GTC（P．Asp319Val）。SIFT功能预测该错义突变将影响蛋白结构。结论该患者发病是由cOMP基因c．956A〉T突变导致，该突变国内外未见报道。

Objective To perform mutation analysis for a female with multiple epiphyseal dysplasia （MED） and provide pre-symptomatic and prenatal diagnosis. Methods Mutation screening of cartilage oligomeric matrix protein （COMP） gene was carried out through targeted next-generation DNA sequencing and Sanger sequencing. Results A novel c. 956 A〉T resulting in substitution of Aspartic acid 319 for Valine （p. Asp319Val） has been identified in exon 9 of the COMP gene in the patient. As predicted by a SIFT software, above mutation can cause damage to the structure of COMP protein. Conclusion A novel c. 956 A〉T substitution mutation has been identified in a patient featuring MED.