1例GNPTAB基因变异致黏脂贮积症Ⅲα/β型患儿的临床和遗传学分析

Clinical and genetic analysis of a patient with mucolipidosisⅢα/βcaused by a variant in the GNPTAB gene

目的对1例表现为骨骼畸形,关节异常,特殊面容,运动障碍,智力障碍的患儿进行遗传学分析,明确其病因。方法提取患儿及其父母、妹妹外周血DNA,应用全外显子组测序技术结合临床表型系统分析相关基因的致病变异,通过Sanger测序对先证者及父母、妹妹进行验证。结果全外显子组测序结果显示患儿的GNPTAB基因第13外显子存在c.2715+1G>A和第9外显子存在c.1090C>T(p.Arg364*)复合杂合变异,分别遗传自父亲和母亲,且变异为已报道的致病性变异,患儿妹妹存在c.1090C>T(p.Arg364*)变异,遗传自母亲。结论GNPTAB基因c.2715+1G>A和c.1090C>T复合杂合变异可能为患儿的致病原因。我们的结果为家系的遗传咨询提供了依据。

Objective To analyze the genetics of a patient with skeletal deformities,joint anomalies,special facial features,motor disorders,and mental retardation,and to clarify the etiology of the disease.Methods The peripheral blood DNA of the patient,his parents and his sister were extracted,and the pathogenic variants of the relevant genes were analyzed by whole exome sequencing(WES)combined with the clinical phenotyping system,and verified by Sanger sequencing in the proband and his family.Results WES showed the presence of c.2715+1G>A in exon 13 and c.1090C>T(p.Arg364*)compound heterozygous variants in exon 9 of the GNPTAB gene in the patient,which were inherited from the father and mother respectively,and the variants were reported to be pathogenic,and the c.1090C>T(p.Arg364*)variant was present in the sister,which was inherited from the mother.Conclusion The compound heterozygous variant of c.2715+1G>A and c.1090C>T in the GNPTAB gene may be the causative agent in the affected child.Our results provide a basis for genetic counseling in the family line.