IDUA基因复合杂合变异导致黏多糖贮积症Ⅰ型一例

Analysis of a child with mucopolysaccharidoses type I due to compound heterozygous variants of IDUA gene

目的对1例黏多糖贮积症Ⅰ型患儿进行临床和遗传学分析。方法对1例因双手十指伸直受限、双下肢屈曲畸形而就诊于骨科门诊的患儿进行基因检测,通过全外显子组测序对患儿进行遗传学分析,并对其父母及两个姐姐进行Sanger测序验证。结果患儿临床表现为面容丑陋、身材矮小、头圆大、颈短、角膜浑浊、骨骼畸形,酶学检测阳性,基因检测发现定位于4号染色体上的IDUA基因存在两处杂合变异,c.1049delA(p.N350Mfs*4)和c.1815dupT(p.V606Cfs*53),这两处杂合变异的家系验证结果显示分别遗传自母亲和父亲,患儿大姐和二姐分别携带这两种致病基因。c.1815dupT为已报道的致病基因,c.1049delA在人类基因数据库中未见收录。结论IDUA基因复合杂合变异是该患儿的遗传学病因,c.1049delA(p.N350Mfs*4)为一个新变异,丰富了该病的变异谱。

Objective To analyze the clinical and genetic characteristics of a child with mucopolysaccharidoses type I.Methods Enzymatic and genetic testing were carried out for the child who was admitted due to contraction of fingers and flexion deformity of lower limbs.The child was subjected to target exome capture sequencing.Candidate variants were verified by Sanger sequencing of the child,her parents and two sisters.Results The child had featured facial dysmorphism,short stature,round head,short neck,corneal turbidity and skeletal deformity.Enzyme test was positive,and genetic testing revealed that she had harbored c.1049delA(p.N350Mfs*4)and c.1815dupT(p.V606Cfs*53)compound heterozygous variants of the IDUA gene,which were inherited from her mother and father,respectively.Her two sisters had each carried one of above variants.c.1815dupT was known to be pathogenic,whilst c.1049delA was not reported in Human Gene Mutation Database.Conclusion The compound heterozygous variants of the IDUA gene probably underlay the disease in this child,among which the c.1049delA(p.N350Mfs*4)is unreported previously.