一个先天性脊柱骨骺发育不良家系致病基因COL2A1突变的研究

摘要

Objective To identify potential disease-causing mutation in the COL2A1 gene in a Chinese family affected with autosomal dominant spondyloepiphyseal dysplasia congenita (SEDC;OMIM 183900) and to analyze the phenotype-genotype correlation.Methods Complete physical,and radiographic examinations of 4 affected individuals from the family were conducted.Genomic DNA was isolated from peripheral blood leukocytes.Whole-exome sequencing was performed using a HiSeq2000 sequencer.All 54 exons and exon-intron boundaries of the COL2A1 gene were amplified by polymerase chain reaction (PCR) and bidirectionally sequenced.Results All of the 4 individuals were found to carry a novel missense mutation of c.2224G＞A (p.Gly687Ser) in the COL2A1 gene,while the same mutation was not found in the normal members of the family and 50 healthy controls.Protein prediction of missense mutation by Polyphen2 and SIFT software indicated severe damage to the function.Conclusion The mutation c.2224G＞A (p.Gly687Ser) of the COL2A1 gene is responsible for this family.There are heterozygous of phenotype for the mutation.%目的 对一个先天性脊柱骨骺发育不良(spondyloepiphyseal dysplasia congenital,SEDC)家系的4位患病成员的COL2A1基因进行突变检测,分析突变形式与临床表型的关系.方法 根据病史、临床表现和骨骼影像学,该家系被诊断为常染色体显性遗传的SEDC.应用聚合酶链反应和直接测序法对该家系的所有成员进行COL2A1基因的突变检测.结果 家系中的4例患者均携带COL2A1基因的一个新的错义突变(c.2224G＞A;p.Gly687Ser),而家系中的正常个体和50名正常对照则未发现相同的变异.Polyphen-2和SIFT生物信息学分析数据高度支持该变异为致病性突变.结论 COL2A1基因c.2224G＞A突变可能导致SEDC.来自同一家系的患者的临床表现存在异质性.