Clinical outcome and genotype analysis of 4 Chinese children with pyruvate kinase deficiency

Abstract Objective: To summarize the clinical features and laboratory examinations of 4 Chinese children with pyruvate kinase deficiency (PKD)，and analyze genomic mutations. Method: Collected and analyzed the clinical data of all children and their parents, and completed the relevant laboratory examinations of all children. Analyzed the sequences of related genes in children by second-generation sequencing technology, and verified the suspected mutations in children's family by Sanger sequencing method or second-generation sequencing technology. Results: A total of 6 mutations in gene PKLR were detected in 4 cases. Except for c.1510C>T (P1) and c.941T>C(P2 and P4), which had been reported in previous studies, the other 4 novel gene mutations were reported for the first time, including a rare homozygous mutation with large fragment deletion. All those gene mutations cause changes in the amino acids encoded by the gene, as well as subsequent changes in protein structure or loss of function. Conclusion: Compound heterozygous or homozygous mutations in the coding region of PKLR gene are the causes of PKD in these 4 Chinese children. The second-generation sequencing technology is an effective means to diagnose PKD. The mutations of c.457-c.462delATCGCC, c.1297T>C, c.1096C>T and Exon4-10del of PKLR reported in this article have not been included in the Thousand Genome Database, dbSNP(v138) and ExAC Database. The PKLR gene mutations found in these children with PKD can provide references for further research of the genetic characteristics of PKD and subsequent gene therapy.