Novel mutations associated with pyruvate kinase deficiency in Brazil
| Autor: | Paulo Augusto Achucarro Silveira, Fernando Ferreira Costa, Jhonathan Angel Araujo Fernandez, Silvia Regina Brandalise, Ana Paula Hitomi Yokoyama, Sara Teresinha Olalla Saad, Maria Carolina Costa Melo Svidnicki, Andrey Santos, Isis Q. Magalhães, Vitória Régia Pereira Pinheiro |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Hemolytic anemia Biology medicine.disease_cause 03 medical and health sciences Autosomal recessive trait symbols.namesake 0302 clinical medicine medicine Immunology and Allergy Missense mutation Gene Pyruvate kinase Genetics Sanger sequencing Mutation PKLR gene lcsh:RC633-647.5 Hematology lcsh:Diseases of the blood and blood-forming organs Red cell disorder medicine.disease 030104 developmental biology symbols 030215 immunology Pyruvate kinase deficiency |
| Zdroj: | Hematology, Transfusion and Cell Therapy, Vol 40, Iss 1, Pp 5-11 (2018) Hematology, Transfusion and Cell Therapy, Volume: 40, Issue: 1, Pages: 11-5, Published: MAR 2018 |
| ISSN: | 2531-1379 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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