Unknown

Dataset Information

0

Alu element insertion in PKLR gene as a novel cause of pyruvate kinase deficiency in Middle Eastern patients.

ABSTRACT: Pyruvate kinase deficiency (PKD) is the most frequent red blood cell enzyme abnormality of the glycolytic pathway and the most common cause of hereditary nonspherocytic hemolytic anemia. Over 250 PKLR-gene mutations have been described, including missense/nonsense, splicing and regulatory mutations, small insertions, small and gross deletions, causing PKD and hemolytic anemia of variable severity. Alu retrotransposons are the most abundant mobile DNA sequences in the human genome, contributing to almost 11% of its mass. Alu insertions have been associated with a number of human diseases either by disrupting a coding region or a splice signal. Here, we report on two unrelated Middle Eastern patients, both born from consanguineous parents, with transfusion-dependent hemolytic anemia, where sequence analysis revealed a homozygous insertion of AluYb9 within exon 6 of the PKLR gene, causing precipitous decrease of PKLR RNA levels. This Alu element insertion consists a previously unrecognized mechanism underlying pathogenesis of PKD.

SUBMITTER: Lesmana H 

PROVIDER: S-EPMC5805577 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Alu element insertion in PKLR gene as a novel cause of pyruvate kinase deficiency in Middle Eastern patients.

Lesmana Harry H   Dyer Lisa L   Li Xia X   Denton James J   Griffiths Jenna J   Chonat Satheesh S   Seu Katie G KG   Heeney Matthew M MM   Zhang Kejian K   Hopkin Robert J RJ   Kalfa Theodosia A TA  

Human mutation 20180111 3

Pyruvate kinase deficiency (PKD) is the most frequent red blood cell enzyme abnormality of the glycolytic pathway and the most common cause of hereditary nonspherocytic hemolytic anemia. Over 250 PKLR-gene mutations have been described, including missense/nonsense, splicing and regulatory mutations, small insertions, small and gross deletions, causing PKD and hemolytic anemia of variable severity. Alu retrotransposons are the most abundant mobile DNA sequences in the human genome, contributing t  ...[more]

Similar Datasets

Unknown Pyruvate kinase deficiency and <i>PKLR</i> gene mutations: Insights from molecular dynamics simulation analysis.
| S-EPMC10904247 | biostudies-literature
Unknown Insertion of an Alu Element in Thyroglobulin Gene as a Novel Cause of Congenital Hypothyroidism.
| S-EPMC7232585 | biostudies-literature
Unknown Insertion of an Alu-like element in MLH1 intron 7 as a novel cause of Lynch syndrome.
| S-EPMC7767547 | biostudies-literature
Unknown Case report: Compound heterozygosity in <i>PKLR</i> gene with a large exon deletion and a novel rare p.Gly536Asp variant as a cause of severe pyruvate kinase deficiency.
| S-EPMC9752143 | biostudies-literature
Unknown Modulation of Malaria Phenotypes by Pyruvate Kinase (PKLR) Variants in a Thai Population.
| S-EPMC4677815 | biostudies-literature
Unknown A novel homozygous missense variant p.D339N in the PKLR gene correlates with pyruvate kinase deficiency in a Pakistani family: a case report.
| S-EPMC8848962 | biostudies-literature
Unknown Addressing the diagnostic gaps in pyruvate kinase deficiency: Consensus recommendations on the diagnosis of pyruvate kinase deficiency.
| S-EPMC7344868 | biostudies-literature
Unknown Molecular heterogeneity of pyruvate kinase deficiency.
| S-EPMC7556514 | biostudies-literature
Unknown Case report: A rare case of pyruvate kinase deficiency and Crigler-Najjar syndrome type II with a novel pathogenic variant of PKLR and UGT1A1 mutation
| S-EPMC10475990 | biostudies-literature
Unknown Alu-element insertion in an OPA1 intron sequence associated with autosomal dominant optic atrophy.
| S-EPMC2820104 | biostudies-literature