新复合杂合突变导致的黏脂贮积症Ⅱα/β患儿一例

A novel compound heterozygous mutation of GNPTAB gene underlying a case with mucolipidosis type Ⅱα/β

目的 分析1例黏脂贮积症Ⅱα/β息儿的临床特征,并应用高通量测序技术对之进行基因检测.方法 收集患儿的临床资料,抽提患儿及其父母的外周血DNA,应用高通量测序技术对患儿进行黏多糖累积症和黏脂贮积症相关基因的检测,用Sanger测序法对筛选出的可疑位点进行验证.结果 患儿的GNPTAB基因存在c.1284+ 1G>T、c.1090C>T(p.Arg364*)复合杂合突变,其父亲为c.1090C>T(p.Arg364*)杂合突变的携带者,母亲为c.1284+1G>T杂合突变的携带者.c.1090C>T(p.Arg364*)为已知的致病突变,c.1284+ 1G>T未见报道的新突变.在50名健康对照中均未发现同样的突变.结论 GNPTAB基因c.1284+1G>T、c.1090C>T(p.Arg364*)复合杂合突变可能是息儿罹息黏脂贮积症Ⅱa/β的主要原因,高通量测序技术对于该病的分子诊断及分型具有重要的价值.

Objective To analyze the clinical features and genetic mutations in a patient with mucolipidosis typeⅡα/βby using next generation sequencing.Methods Clinical data of the patient was collected.Genomic DNA of the patient and her parents was extracted by a standard method.The patient was subjected to targeted sequencing using an Ion Ampliseq panel which included genes related to mucolipidosis and mucopolysaccharidosis.Suspected mutations were verified by Sanger sequencing.Results A compound heterozygous mutation c.1284+1G>T、c.1090C>T(p.Arg364*)was detected in the patient,which were respectively inherited from her mother and father.No other disease-causing mutation was detected in the patient.GNPTAB c.1090C>T is known to be pathogenic,while GNPTAB c.1284+1G>T is a novel mutation.The same mutations were not detected among 50 healthy controls.Conclusion The compound heterozygous mutation c.1284+1G>T and c.1090C>T(p.Arg364*)of GNPTAB gene probably account for the mucolipidosis typeⅡα/βin the patient.NGS technique has a great value for the molecular diagnosis and typing of mucolipidosis.