一例硫胺素代谢功能障碍综合征5型患儿的临床特点及遗传学分析

Clinical and genetic analysis of a case with Thiamine metabolism dysfunction syndrome 5

目的报告1例硫胺素代谢功能障碍综合征5型患儿的临床表现及基因特征。方法收集患儿的临床表现、实验室检查和家族史等资料,并采集患儿及其父母外周血样,进行全外显子组高通量测序,并验证该位点变异后对其TPK1酶活性的影响。结果患儿为4岁男孩,学龄前起病,以共济失调为首发症状。高通量测序发现其携带TPK1基因c.382G>A(p.Leu128Phe)纯合变异,既往未见报道,患儿父母分别携带该变异。人工合成的该TPK1变异序列显示,与对照组相比,TPK1基因在该位点的变异导致TPK1酶活性下降了30.9%。结论确诊了1例硫胺素代谢功能障碍综合征5型患儿,丰富了TPK1基因变异数据库。

Objective To report the clinical manifestation and genetic characteristics of a child with Thiamine metabolism dysfunction syndrome 5.Methods Clinical data and genetic results were collected and analyzed.Peripheral blood samples of the child and their parents was collected for whole exome sequencing,and the functional effect of the variants on the TPK1 enzyme activity was verified by an in vitro assay.Results A four-year-old boy presented with preschool onset of ataxia were characterized.High-throughput sequencing identified a novel homozygous variant of TPK1 gene c.382G>A(p.Leu128Phe).His father and mother were both found carrying the variant.The variant protein showed a 30.9%reduction in TPK1 enzyme activity compared with the wildtype.Conclusion A novel pathogenic variant has been identified in a boy with thiamine metabolic dysfunction syndrome type 5.