COL1A1新发突变致儿童成骨不全症1例报道并文献复习

A case report of osteogenesis imperfecta in children with novel COL1A1 gene mutation and literature review

目的分析一例I型成骨不全症(osteogenesis imperfecta,OI)患儿的临床特点,并研究患者及其家系的基因突变情况及致病性鉴定。方法详细询问病史,分析骨转换指标、骨密度、骨骼X线特点。采用高通量测序法,对患儿骨病检测包225个相关致病基因各外显子编码区域的序列变异情况进行检测分析,采用PCR结合Sanger测序的方法验证突变位点变异情况。结果骨标志物提示高转换水平,影像学提示骨量低下,四肢长骨纤细、骨皮质变薄,基因检测发现患儿COL1A1基因编码区杂合变异c.2911_2912insAG(p.G971Efs*138),经Mutation Taster预测显示为致病性突变。先证者母亲、父亲以及妹妹均未携带该突变基因。结论发现了OI患者COL1A1基因新的突变位点c.2911_2912insAG(p.G971Efs*138),丰富了中国人OI群体COL1A1基因致病突变谱。

Objective To analyze clinical features of an osteogenesis imperfecta(OI)child,and to study the gene mutation and pathogenicity identification of the patient and his family.Methods The medical history was inquired in detail.Bone turnover markers,bone mineral density,and bone X-ray characteristics were analyzed.The sequence variation of each exon coding region of 225 related pathogenic genes of the patient was detected and analyzed using high throughput sequencing technology.The mutation site was verified with PCR combining with Sanger sequencing.Results Bone marker result suggested high turnover level.Image examination result suggested low bone mass,slender limb bones,and thinning bone cortex.The heterozygous variation of c.2911_2912insAG(p.G971Efs*138)was found in the coding region of COL1A1 gene.It was predicted as a disease-causing mutation by a mutation taster.The mutant gene was not carried by the mother,father,and sister of the patient.Conclusion A new mutation site c.2911_2912insAG(p.g971efs*138)of COL1A1 gene in OI patients is found,which enriches the pathogenic mutation spectrum of COL1A1 gene in Chinese OI population.