Revista Brasileira de Hematologia e Hemoterapia Revista Brasileira de Hematologia e Hemoterapia
Hematology,Transfusion and Cell Therapy 2018;40:5-11 DOI: 10.1016/j.bjhh.2017.08.007
Original article
Novel mutations associated with pyruvate kinase deficiency in Brazil
Maria Carolina Costa Melo Svidnickia, Andrey Santosb, Jhonathan Angel Araujo Fernandezc, Ana Paula Hitomi Yokoyamaa, Isis Quezado Magalhãesd, Vitoria Regia Pereira Pinheiroe, Silvia Regina Brandalisef, Paulo Augusto Achucarro Silveirag, Fernando Ferreira Costaa,b, Sara Teresinha Olalla Saada,b,,
a Centro de Hematologia e Hemoterapia da Universidade Estadual de Campinas (HEMOCENTRO/UNICAMP), Campinas, SP, Brazil
b Departamento de Medicina Interna da Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
c Centro de Biologia Molecular e Engenharia Genética da Universidade Estadual de Campinas (CBMEG/UNICAMP), Campinas, SP, Brazil
d Hospital da Criança de Brasília (HCB), Brasília, DF, Brazil
e Centro Integrado de Pesquisas Onco-Hematológicas na Infância da Universidade Estadual de Campinas (CIPOI/UNICAMP), Campinas, SP, Brazil
f Centro Infantil Bondrini, Campinas, SP, Brazil
g Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
Recebido 15 Fevereiro 2017, Aceitaram 02 Agosto 2017
Abstract
Background

Pyruvate kinase deficiency is a hereditary disease that affects the glycolytic pathway of the red blood cell, causing nonspherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait and shows a marked variability in clinical expression. This study reports on the molecular characterization of ten Brazilian pyruvate kinase-deficient patients and the genotype–phenotype correlations.

Method

Sanger sequencing and in silico analysis were carried out to identify and characterize the genetic mutations. A non-affected group of Brazilian individuals were also screened for the most commonly reported variants (c.1456C>T and c.1529G>A).

Results

Ten different variants were identified in the PKLR gene, of which three are reported here for the first time: p.Leu61Gln, p.Ala137Val and p.Ala428Thr. All the three missense variants involve conserved amino acids, providing a rationale for the observed enzyme deficiency. The allelic frequency of c.1456C>T was 0.1% and the 1529G>A variant was not found.

Conclusion

This is the first comprehensive report on molecular characterization of pyruvate kinase deficiency from South America. The results allowed us to correlate the severity of the clinical phenotype with the identified variants.

Keywords
Red cell disorder, Pyruvate kinase, Mutation, Hemolytic anemia, PKLR gene
Hematology,Transfusion and Cell Therapy 2018;40:5-11 DOI: 10.1016/j.bjhh.2017.08.007