一个先天性糖基化病家系的临床特征和致病变异分析

Analysis of clinical features and pathogenic variants in a Chinese pedigree affected with congenital glycosylation disease

目的探讨一个先天性糖基化病家系的临床特点及遗传学特征。方法对该家系两例患者的临床资料进行分析,对家系成员进行全外显子组测序,并用Sanger测序对疑似致病变异进行验证。结果先证者及其弟弟均携带PMM2基因复合杂合突变,其中第5外显子的c.395T>C(p.I132T)为已知致病突变,第5内含子的c.448-1delAG为既往未见报道的新突变。结论位于PMM2基因第5内含子的c.448-1delAG的剪接位点变异为先天性糖基化病新发现的致病变异类型。

Objective To explore the clinical features and genetic basis for a Chinese pedigree diagnosed with congenital glycosylation disease(CGD).Methods Clinical manifestations of two brothers were analyzed.Whole exome sequencing was carried out for the sib pair.Suspected variants were verified by Sanger sequencing.Results Both the proband and her younger brother were found to carry compound heterozygous variants of the PMM2 gene,which included a known pathogenic mutation of c.395T>C(p.I132T)and a previously unreported c.448-1(delAG)in the 5′end of exon 6 of the gene.Conclusion The compound heterozygous variants of the PMM2 gene probably underlay the CGD in the sib pair.