PKLR Arg498His/Ile314Thr复合杂合突变致重型丙酮酸激酶缺乏症1例并文献复习

Severe pyruvate kinase deficiency caused by PKLR Arg498His/Ile314Thr compound heterozygous mutation:one case report and literature review

目的:探讨丙酮酸激酶缺乏症(PKD)的临床及遗传学特点。方法:回顾分析1例PKD患儿的临床病例资料,采用疾病相关基因目标序列捕获和二代测序技术,筛选患儿及其父母基因突变类型,再用Sanger测序法进行验证。复习相关文献总结PKD的临床及遗传学特点。结果:入院时,患儿年龄为1个月14 d,主要临床表现为生后即出现高胆红素血症,皮肤巩膜重度黄染,多次血常规检查提示重度贫血。基因检测结果显示,PKLR基因复合杂合突变:10号外显子上的c.1493G>A(Arg498His)突变以及7号外显子上的c.941T>C(Ile314Thr)。经预测两种突变对蛋白功能影响较大,均为致病突变,其中,Arg498His是内含子A与外显子3边界处的剪接位点突变。结论:PKD的血液学特征不明显,基因检测可帮助确诊。根据ACMG指南PKLR Arg498His、PKLR Arg498His均评为致病突变。PKLR Arg498His/Arg498His复合杂合突变可导致重型PKD。

Objective:To explore the clinical and genetic characteristics of pyruvate kinase deficiency(PKD).Methods:The clinical data of a child with PKD were analyzed retrospectively.The gene mutation types of the child and his parents were screened by disease-related gene target sequence and second-generation sequencing,and then verified by Sanger sequencing.Reviewed the related literature and summarized the clinical and genetic characteristics of PKD.Results:The age of the child was 1 month and 14 days when he was admitted to hospital.The main clinical manifestations were hyperbilirubinemia,severe yellow staining of skin and sclera,and severe anemia revealed by multiple blood tests.The results of gene detection showed that the compound heterozygous mutation of PKLR gene was c.1493G>A(Arg498His)on exon 10 and c.941T>C(Ile314Thr)on exon 7.It was predicted that the two mutations had great influence on the protein function,and both of them were pathogenic mutations,in which Arg498His was the splice site mutation at the boundary between intron A and exon 3.Conclusion:The hematological characteristics of PKD are unobvious,and genetic detection can help for diagnosing.PKLR Arg498His and PKLR Arg498His were considered as pathogenic mutations according to ACMG guidelines.PKLR Arg498His/Arg498His compound heterozygous mutation can lead to severe PKD.