title: Red blood cell PK deficiency: An update of PK-LR gene mutation database.
abstract: Pyruvate kinase (PK) deficiency is known as being the most common cause of chronic nonspherocytic hemolytic anemia (CNSHA). Clinical PK deficiency is transmitted as an autosomal recessive trait, that can segregate neither in homozygous or in a compound heterozygous modality, respectively. Two PK genes are present in mammals: the pyruvate kinase liver and red blood cells (PK-LR) and the pyruvate kinase muscle (PK-M), of which only the first encodes for the isoenzymes normally expressed in the red blood cells (R-type) and in the liver (L-type). Several reports have been published describing a large variety of genetic defects in PK-LR gene associated to CNSHA. Herein, we present a review of about 250 published mutations and six polymorphisms in PK-LR gene with the corresponding clinical and molecular data. We consulted the PubMed website for searching mutations and papers, along with two main databases: the Leiden Open Variation Database (LOVD, https://grenada.lumc.nl/LOVD2/mendelian_genes/home.php?select_db=PKLR) and Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/gene.php?gene=PKLR) for selecting, reviewing and listing the annotated PK-LR gene mutations present in literature. This paper is aimed to provide useful information to clinicians and laboratory professionals regarding overall reported PK-LR gene mutations, also giving the opportunity to harmonize data regarding PK-deficient individuals.
authors.affiliation: Laboratory of Clinical Molecular and Personalized Diagnostics, Department of Laboratory Medicine, "A Gemelli" Hospital, Catholic University, Largo Agostino Gemelli 8, Roma, Italy. Electronic address: giuliacanu@gmail.com.
authors.forename: Giulia
authors.initials: G
authors.lastname: Canu
authors.affiliation: Laboratory of Clinical Molecular and Personalized Diagnostics, Department of Laboratory Medicine, "A Gemelli" Hospital, Catholic University, Largo Agostino Gemelli 8, Roma, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: De Bonis
authors.affiliation: Laboratory of Clinical Molecular and Personalized Diagnostics, Department of Laboratory Medicine, "A Gemelli" Hospital, Catholic University, Largo Agostino Gemelli 8, Roma, Italy. Electronic address: angelo.minucci@virgilio.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Minucci
authors.affiliation: Laboratory of Clinical Molecular and Personalized Diagnostics, Department of Laboratory Medicine, "A Gemelli" Hospital, Catholic University, Largo Agostino Gemelli 8, Roma, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Capoluongo
mesh_terms: D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000818:Animals; D030541:Databases, Genetic; D004912:Erythrocytes / Q000201:enzymology* / Q000473:pathology; D005808:Genes, Recessive; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000473:pathology; D009132:Muscles / Q000201:enzymology / Q000473:pathology; D009154:Mutation; D011110:Polymorphism, Genetic; D011770:Pyruvate Kinase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D015323:Pyruvate Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D007527:Isoenzymes; D011770:Pyruvate Kinase
keywords: PK-LR gene; Pyruvate kinase; hemolysis