Red blood cell PK deficiency: An update of PK-LR gene mutation database

Canu, Giulia; Bonis, Maria De; Minucci, Angelo; Capoluongo, Ettore

doi:10.1016/j.bcmd.2015.12.009

Cited by 70 publications

(70 citation statements)

References 69 publications

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“…There are no known mutations associated with PK deficiency that affect the amino acids listed above that make contact with AG-348. 21 Next, we evaluated the effects of AG-348 on PK activity in intact human RBCs. We purified RBCs from whole blood from healthy donors and incubated them with AG-348 overnight.…”

Section: Resultsmentioning

confidence: 99%

AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency

Kung

Hixon

Kosinski

et al. 2017

Blood

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Section: Resultsmentioning

confidence: 99%

AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency

Kung

Hixon

Kosinski

et al. 2017

Blood

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“…In contrast to other IHAs, the morphology of the RBCs shows no specific abnormalities. Diagnosis is based on the detection of reduced specific enzyme activity and molecular characterization of the defect at the DNA level [4950]. …”

Section: Rbc Enzymopathymentioning

confidence: 99%

“…Over 200 PKLR mutations have been described [6566]. Up to 70% of PK-deficient alleles carry a missense mutation followed by splicing and stop codon mutations (13% and 5%, respectively; www.lovd.nl/pklr) [50]. Although a genotype-phenotype relationship has not yet been unveiled [67], patients with homozygous null mutations display severe phenotypes including intrauterine growth retardation, severe anemia at birth, and blood transfusion dependence [68].…”

Section: Rbc Enzymopathymentioning

confidence: 99%

Diagnostic approaches for inherited hemolytic anemia in the genetic era

2017

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Inherited hemolytic anemias (IHAs) are genetic diseases that present with anemia due to the increased destruction of circulating abnormal RBCs. The RBC abnormalities are classified into the three major disorders of membranopathies, hemoglobinopathies, and enzymopathies. Traditional diagnosis of IHA has been performed via a step-wise process combining clinical and laboratory findings. Nowadays, the etiology of IHA accounts for germline mutations of the responsible genes coding for the structural components of RBCs. Recent advances in molecular technologies, including next-generation sequencing, inspire us to apply these technologies as a first-line approach for the identification of potential mutations and to determine the novel causative genes in patients with IHAs. We herein review the concept and strategy for the genetic diagnosis of IHAs and provide an overview of the preparations for clinical applications of the new molecular technologies.

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“…10 exons are shared by two isoforms, while exon 1 and 2 are specific for the erythrocytic and hepatic isoenzyme, respectively. Over 260 different PKLR mutations have been associated with hemolytic anemias . PK deficiency is transmitted in AR fashion with both homozygous and compound heterozygous mutations reported.…”

Section: Rbc Enzyme Defectsmentioning

confidence: 99%

Molecular diagnostic update in hereditary hemolytic anemia and neonatal hyperbilirubinemia

Rets

Clayton

Christensen

et al. 2019

Int J Lab Hematology

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Hereditary hemolytic anemia (HHA) is a group of genetically and phenotypically heterogeneous disorders characterized by premature destruction of red blood cells (RBCs) with clinical manifestations ranging from asymptomatic to marked hemolytic anemia. There are three main categories of HHA: (a) RBC membrane defects; (b) hemoglobinopathies/thalassemias; and (c) RBC enzyme deficiencies. Hyperbilirubinemia is a frequent consequence of hemolytic anemia and can lead to bilirubin‐associated neurotoxicity in neonates and to jaundice, and formation of gall stones in adults. Hyperbilirubinemia can also be caused by impaired bilirubin conjugation due to polymorphisms and mutations in genes involved in bilirubin metabolism (eg, UGT1A1). Neonates with HHA and co‐inherited variants impairing bilirubin conjugation are at increased risk of bilirubin‐associated toxicity. Prior to the advent of next‐generation sequencing (NGS), molecular diagnosis of these disorders was limited to targeted single gene Sanger sequencing. However, NGS is making its way into the standard diagnostic workup of complex and multigene disorders like HHA. This review will focus on the molecular updates of HHA with particular focus on the neonatal and pediatric population.

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Red blood cell PK deficiency: An update of PK-LR gene mutation database

Cited by 70 publications

References 69 publications

AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency

AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency

Diagnostic approaches for inherited hemolytic anemia in the genetic era

Molecular diagnostic update in hereditary hemolytic anemia and neonatal hyperbilirubinemia

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