SÀNG LỌC DI TRUYỀN TIỀN LÀM TỔ CHO MỘT CA BỆNH THIẾU MEN PYRUVATE KINASE

Abstract

Background: Pyruvate kinase deficiency (PKD) is an autosomal recessive genetic disorder caused by mutations in the PKLR gene. Mutations in this gene are a common cause of chronic hemolytic anemia. People with this disorder suffer from reduced quality of life and economic burden. Preimplantation genetic testing for monogenic disorders (PGT-M) is an option for families carrying a genetic mutation to select embryos with out the mutation to transfer to have healthy babies. Case report: A couple whose daughter was diagnosed with hemolytic anemia disease wanted to undergo PGT-M. Molecular biological techniques including MLPA, Sanger sequencing, NGS, and genetic linkage analysis were used to identify the gene mutation in the family as well as identify embryos that did not carry the gene mutation. Results: Two mutations c.941T>C (p.Ile314Thr) and deletion from exon 3 to exon 9 in the PKLR gene were detected in this family, which are associated with pyruvate kinase deficiency. Of the four biopsied embryos for preimplantation genetic testing, only two embryos without chromosomal aneuploidy were did PGT-M testing futher. As a result, one embryo was a compound heterozygote, one embryo was free with both mutations in the PKLR gene and was transferred into the mother's uterus. Conclusions: Accurate detection of pathogenic mutations is important in counseling and performing PGT-M testing. Combining direct analysis with genetic linkage analysis increases the reliability of PGT-M results. Successfully developing a PGT-M procedure for mutations in the PKLR gene helps the patient's family have a chance of having a child with out the genetic disease.