Molecular heterogeneity of pyruvate kinase deficiency.
Molecular heterogeneity of pyruvate kinase deficiency.
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DOI：
10.3324/haematol.2019.241141
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发表时间：
2020-09-01
期刊：
影响因子：
10.1
通讯作者：
Fermo E
中科院分区：
文献类型：
--
作者：
Bianchi P;Fermo E
红细胞丙酮酸激酶（PK）缺陷是与先天性非球形细胞溶血性贫血相关的最常见的糖酵解缺陷。该疾病以常染色体隐性遗传方式传播，由 PKLR 基因突变引起，具有分子和临床异质性的特点；贫血范围从轻度或完全代偿性溶血到危及生命的形式，需要新生儿换血和/或随后定期输血支持；并发症包括胆结石、肺动脉高压、髓外造血和铁超载。自1991年鉴定出第一个导致PK缺陷的致病变异以来，已报道了300多种不同的变异，并且对分子机制和基因型-表型相关性的存在进行了深入研究。近年来，基因分析、新一代测序技术和个性化医疗的进步为先天性溶血性贫血的诊断和分子机制研究开辟了重要领域，基因分型已成为获得新疗法和评估疾病状态和进展的先决条件。本综述研究了 PK 缺陷的广泛分子异质性，重点关注基因型和新获得的致病性非典型变异的诊断影响。还讨论了理解基因型-表型相关性的最新进展和弱点，以及它在 PK 缺乏新治疗机会方面的实际用途。
Red cell pyruvate kinase (PK) deficiency is the most common glycolytic defect associated with congenital non-spherocytic hemolytic anemia. The disease, transmitted as an autosomal recessive trait, is caused by mutations in the PKLR gene and is characterized by molecular and clinical heterogeneity; anemia ranges from mild or fully compensated hemolysis to life-threatening forms necessitating neonatal exchange transfusions and/or subsequent regular transfusion support; complications include gallstones, pulmonary hypertension, extramedullary hematopoiesis and iron overload. Since identification of the first pathogenic variants responsible for PK deficiency in 1991, more than 300 different variants have been reported, and the study of molecular mechanisms and the existence of genotype-phenotype correlations have been investigated in-depth. In recent years, during which progress in genetic analysis, next-generation sequencing technologies and personalized medicine have opened up important landscapes for diagnosis and study of molecular mechanisms of congenital hemolytic anemias, genotyping has become a prerequisite for accessing new treatments and for evaluating disease state and progression. This review examines the extensive molecular heterogeneity of PK deficiency, focusing on the diagnostic impact of genotypes and new acquisitions on pathogenic non-canonical variants. The recent progress and the weakness in understanding the genotype-phenotype correlation, and its practical usefulness in light of new therapeutic opportunities for PK deficiency are also discussed.
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DOI：
10.1016/j.bjhh.2017.08.007
发表时间：
2018-03-01
期刊：
Hematology, Transfusion and Cell Therapy
影响因子：
--
作者：
Svidnicki, Maria Carolina Costa Melo;Santos, Andrey;Saad, Sara Teresinha Olalla
通讯作者：
Saad, Sara Teresinha Olalla
DOI：
10.1159/000459004
发表时间：
1975-01-01
期刊：
ENZYME
影响因子：
--
作者：
BOIVIN, P;GALAND, C;KAHN, A
通讯作者：
KAHN, A
影响因子：
1.9
作者：
Alli, Nazeer;Coetzee, Marius;Thein, Swee Lay
通讯作者：
Thein, Swee Lay
影响因子：
3
作者：
Del Orbe Barreto, R.;Arrizabalaga, B.;Ribeiro, M. L.
通讯作者：
Ribeiro, M. L.
影响因子：
6.5
作者：
Agarwal, Archana M.;Nussenzveig, Roberto H.;Christensen, Robert D.
通讯作者：
Christensen, Robert D.