Genetic diagnosis of erythrocyte pyruvate kinase deficiency and discovery of PKLR gene novel mutations / 中华实用儿科临床杂志

ABSTRACT

Objective To investigate the clinical symptoms of pyruvate kinase deficiency (PKD) and the new mutation type of PKLR gene in 3 cases of PKD,and to explore the method for PKD gene diagnosis.Methods Sequencing of blood system-related genes in 3 children was performed by target sequence capture and high-throughput sequencing technology,and the protein function of mutant gene was forecasted,after detecting the pathogenicity of the patients,these genotypes were confirmed by Sanger sequencing.Results In the 3 children,5 types of PKLR gene mutations were founddouble heterozygous mutations c.1529G ＞ A(p.R510Q) and c.1031T ＞ G(p.I344S),homozygous mutation c.847G ＞ T (p.V283F),double heterozygous mutations c.979delC (p.L327fs)and c.604_617del (p.V202fs).PKLR gene c.1529G ＞ A(p.R510Q) mutation had been reported previously,and the other four mutations were new.c.1031T ＞ G (p.I344S) and c.847G ＞ T (p.V283F) was possibly pathogenic mutation,which meant that the probability of mutation of this gene was more than 90％ and c.979delC (p.L327fs) and c.604 _617del (p.V202fs) variation was a pathogenic variation.These 5 mutations had a greater effect on protein function,and all ofthem were pathogenic mutations.Conclusion Since PKD patients are difficult to be diagnosed clinically,PKLR gene variation can be detected by target sequence capture and high throughput sequencing technology,and the pathogenicity of the new mutant is evaluated.