Novel mutations associated with pyruvate kinase deficiency in Brazil
Novel mutations associated with pyruvate kinase deficiency in Brazil
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DOI：
10.1016/j.bjhh.2017.08.007
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发表时间：
2018-03-01
期刊：
影响因子：
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通讯作者：
Saad, Sara Teresinha Olalla
中科院分区：
文献类型：
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作者：
Svidnicki, Maria Carolina Costa Melo;Santos, Andrey;Saad, Sara Teresinha Olalla
背景：丙酮酸激酶缺乏症是一种遗传性疾病，会影响红细胞的糖酵解途径，导致非球形红细胞溶血性贫血。该疾病作为常染色体隐性遗传特征传播，并在临床表现上表现出显着的变异性。本研究报告了十名巴西丙酮酸激酶缺陷患者的分子特征以及基因型-表型相关性。方法：进行桑格测序和计算机分析来鉴定和表征基因突变。还对一组未受影响的巴西个体进行了最常见报告变异（c.1456C>T 和 c.1529G>A）的筛查。结果：在 PKLR 基因中鉴定出 10 种不同的变异，其中 3 种是首次报道：p.Leu61Gln、p.Ala137Val 和 p.Ala428Thr。所有三种错义变体都涉及保守氨基酸，为观察到的酶缺乏提供了理论依据。 c.1456C>T等位基因频率为0.1%，未发现1529G>A变异体。结论：这是南美洲第一份关于丙酮酸激酶缺陷的分子表征的综合报告。结果使我们能够将临床表型的严重程度与已识别的变异相关联。 (C) 2017 年巴西血液学协会、Hemoterapia e Terapia Cellular。由爱思唯尔编辑有限公司出版。
Background: Pyruvate kinase deficiency is a hereditary disease that affects the glycolytic pathway of the red blood cell, causing nonspherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait and shows a marked variability in clinical expression. This study reports on the molecular characterization of ten Brazilian pyruvate kinase- deficient patients and the genotype-phenotype correlations.Method: Sanger sequencing and in silico analysis were carried out to identify and characterize the genetic mutations. A non-affected group of Brazilian individuals were also screened for the most commonly reported variants (c.1456C>T and c.1529G>A).Results: Ten different variants were identified in the PKLR gene, of which three are reported here for the first time: p.Leu61Gln, p.Ala137Val and p.Ala428Thr. All the three missense variants involve conserved amino acids, providing a rationale for the observed enzyme deficiency. The allelic frequency of c.1456C>T was 0.1% and the 1529G>A variant was not found.Conclusion: This is the first comprehensive report on molecular characterization of pyruvate kinase deficiency from South America. The results allowed us to correlate the severity of the clinical phenotype with the identified variants. (C) 2017 Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda.