Novel mutations associated with pyruvate kinase deficiency in Brazil.

Autor:	Svidnicki MCCM; Centro de Hematologia e Hemoterapia da Universidade Estadual de Campinas (HEMOCENTRO/UNICAMP), Campinas, SP, Brazil., Santos A; Departamento de Medicina Interna da Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil., Fernandez JAA; Centro de Biologia Molecular e Engenharia Genética da Universidade Estadual de Campinas (CBMEG/UNICAMP), Campinas, SP, Brazil., Yokoyama APH; Centro de Hematologia e Hemoterapia da Universidade Estadual de Campinas (HEMOCENTRO/UNICAMP), Campinas, SP, Brazil., Magalhães IQ; Hospital da Criança de Brasília (HCB), Brasília, DF, Brazil., Pinheiro VRP; Centro Integrado de Pesquisas Onco-Hematológicas na Infância da Universidade Estadual de Campinas (CIPOI/UNICAMP), Campinas, SP, Brazil., Brandalise SR; Centro Infantil Bondrini, Campinas, SP, Brazil., Silveira PAA; Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil., Costa FF; Centro de Hematologia e Hemoterapia da Universidade Estadual de Campinas (HEMOCENTRO/UNICAMP), Campinas, SP, Brazil; Departamento de Medicina Interna da Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil., Saad STO; Centro de Hematologia e Hemoterapia da Universidade Estadual de Campinas (HEMOCENTRO/UNICAMP), Campinas, SP, Brazil; Departamento de Medicina Interna da Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil. Electronic address: sara@unicamp.br.
Jazyk:	angličtina
Zdroj:	Hematology, transfusion and cell therapy [Hematol Transfus Cell Ther] 2018 Jan - Mar; Vol. 40 (1), pp. 5-11. Date of Electronic Publication: 2017 Nov 26.
DOI:	10.1016/j.bjhh.2017.08.007
Abstrakt:	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. (Copyright © 2017 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu