一罕见家系DPH1基因新型复合杂合突变的遗传学检测分析

Genetic analysis of a novel compound heterozygous mutation of DPH1 gene in a rare family

目的对一家系中2例发育迟缓伴身材矮小、特殊面容和头发稀疏的遗传学分析。方法采集家庭成员病历资料及外周血样本,应用靶向捕获-高通量测序(WES)和Sanger测序技术对先证者及家系成员验证,MutationTaster、PRONEAN软件对该突变进行致病性预测。结果测序结果显示2例病例DPH1基因第7、10号外显子均存在c.708T>G和c.1046G>A复合杂合突变,分别遗传自父母双方,DPH1基因c.708T>G变异导致第236位天冬氨酸变为谷氨酸(p.Asp236Glu),c.1046G>A(p.Arg349His)变异导致第349位精氨酸变为组氨酸,生物信息学分析预测二者均为致病突变。结论2例患者均存在相同DPH1基因复合杂合突变,主要临床表型与基因型基本相符,该基因的错义突变是导致患者的发病原因,新突变丰富了DPH1基因突变普,采用高通量测序技术可以辅助临床诊断,明确其致病基因,为遗传咨询提供理论依据。

Objective To analyze the genetics of two cases of growth retardation with short stature,special face and sparse hair in a family.Methods The data of family members and peripheral blood samples were collected,and the proband and family members were verified by targeted capture high-throughput sequencing(WES)and Sanger sequencing technology.The pathogenicity of the mutation was predicted by MutationTaster and PRONEAN software.Results The Sequencing results showed that there were compound heterozygous mutations c.708 t>G and c.1046 g>A in exon 7 and 10 ofDPH1 gene in both patients,which were inherited from both parents.The c.708 T>G mutation of theDPH1 gene resulted in the 236 thaspartate to glutamate(p.Asp236 Glu),and c.1046 G>A(p.Arg349 His)mutation resulted in the 349 thposition of arginine to histidine.Bioinformatics analysis predicted that both of them were pathogenic mutations.Conclusion Both patients have the same compound heterozygous mutation in theDPH1 gene,and the main clinical phenotype is basically consistent with the genotype.The missense mutation of this gene is the cause of the patient.s pathogenesis,and the new mutation enriches theDPH1 gene mutation spectrum.High throughput sequencing technology can be used to assist clinical diagnosis and identify its pathogenic genes,so as to provide a theoretical basis for genetic counseling.