Molecular basis of pyruvate kinase deficiency among Tunisians: description of new mutations affecting coding and noncoding regions in the PKLR gene

Summary Introduction Pyruvate kinase (PK) deficiency is one of the most common hereditary nonspherocytic hemolytic anemias worldwide with clinical manifestations ranging from mild to severe hemolysis. However, investigation of this enzymopathy is lacking in Tunisia. We report here a pioneer investig...

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Published in:	International Journal of Laboratory Hematology Vol. 39; no. 2; pp. 223 - 231
Main Authors:	Jaouani, M., Manco, L., Kalai, M., Chaouch, L., Douzi, K., Silva, A., Macedo, S., Darragi, I., Boudriga, I., Chaouachi, D., Fitouri, Z., Van Wijk, R., Ribeiro, M. L., Abbes, S.
Format:	Journal Article
Language:	English
Published:	England Wiley Subscription Services, Inc 01-04-2017 Wiley
Subjects:	Anemia Anemia, Hemolytic - etiology Anemia, Hemolytic - genetics Anemia, Hemolytic, Congenital Nonspherocytic - etiology Anemia, Hemolytic, Congenital Nonspherocytic - genetics DNA Mutational Analysis DNA sequencing Erythrocytes Erythrocytes - enzymology Genetic Association Studies Genetic disorders genotype–phenotype correlation Hemolysis Hemolytic anemia Human health and pathology Humans Laboratories Life Sciences Missense mutation Models, Molecular Molecular modelling Mutation Mutation, Missense - genetics Neonates PKLR mutations Pyruvate kinase Pyruvate Kinase - deficiency Pyruvate Kinase - genetics Pyruvate Metabolism, Inborn Errors - etiology Pyruvate Metabolism, Inborn Errors - genetics Pyruvic acid Studies Tunisia - epidemiology Tunisian families Tunisian families PKLR mutations Pyruvate kinase deficiency genotype-phenotype correlation hemolytic anemia
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Summary:	Summary Introduction Pyruvate kinase (PK) deficiency is one of the most common hereditary nonspherocytic hemolytic anemias worldwide with clinical manifestations ranging from mild to severe hemolysis. However, investigation of this enzymopathy is lacking in Tunisia. We report here a pioneer investigation of PK deficiency among Tunisian cases referred to our laboratory for biological analysis of unknown cause of hemolytic anemia. Methods Two hundred and fifty‐three patients with unknown cause of hemolytic anemia have been addressed to our laboratory in order to investigate for red blood cells genetic disorders. Red cell enzyme activities were measured by standard methods, and molecular analysis was performed by DNA sequencing. The interpretation of mutation effect and the molecular modeling were performed by using specific software. Results Six different PKLR mutations were found (c.966‐1G>T; c.965+1G>A; c.721G>T; c.1163C>A; c.1456C>T; c.1537T>A), among which four are described for the first time. Genotype–phenotype correlations for the novel missense mutations were investigated by three‐dimensional structure analysis. Conclusion This study provides important data of PK deficiency among Tunisians. It might be followed by a large neonatal screening to determine the spectrum of PK mutations and identify potential deficient patients for an early medical follow‐up.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1751-5521 1751-553X 1365-2257
DOI:	10.1111/ijlh.12610