Identification of a novel de novo ANK1 R1426* nonsense mutation in a Chinese family with hereditary spherocytosis by NGS.
Identification of a novel de novo ANK1 R1426* nonsense mutation in a Chinese family with hereditary spherocytosis by NGS.
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DOI：
10.18632/oncotarget.18243
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发表时间：
2017-11-14
期刊：
影响因子：
--
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Wang X;Yi B;Mu K;Shen N;Zhu Y;Hu Q;Lu Y
遗传性球形红细胞增多症（Hereditary spherocytosis，HS）是一种遗传性异质性溶血性贫血，以外周血涂片上出现球形红细胞为特征，临床表现为无症状至严重贫血，且依赖输血的患者。迄今为止，已经确定了至少五个基因（ANK 1、EPB 42、SLC 4A 1、SPTA 1和SPTB）的突变，并且ANK 1基因的突变负责大多数所有HS病例。本研究应用靶向下一代测序（NGS）技术，在一个中国家系中发现了一个新的ANK 1 c.4276C>T（p.R1426*）无义突变，该家系患者临床诊断为外周血中球形红细胞仅占10%，并接受了脾切除术。桑格测序进一步证实，只有该患者携带杂合ANK 1 c.4276 C>T无义突变，而其父母和年幼的弟弟均未携带该突变。此外，与遗传学研究结果一致，脾切除术后贫血得到改善。红细胞从术前的2.74 × 1012/L增加到术后1个月的4.76 × 1012/L，血红蛋白从66 g/L增加到126 g/L。这是首次报道ANK 1 c.4276C>T（p.R1426*）杂合无义突变导致HS。我们的研究结果也表明，有针对性的NGS可能提供一个强大的方法，快速遗传检测HS。
Hereditary spherocytosis (HS) is an inherited heterogeneous hemolytic anemia, characterized by the presence of spherical-shaped erythrocytes on the peripheral blood smear, and the clinical manifestation ranges from asymptomatic to severely anemic, and transfusion-dependent patients. Mutations in at least five genes (ANK1, EPB42, SLC4A1, SPTA1, and SPTB) have been identified so far, and mutations of ANK1 gene are responsible for the majority of all HS cases. In this study, targeted next generation sequencing (NGS) was applied to identify a novel de novo ANK1 c.4276C>T (p.R1426*) nonsense mutation in a Chinese family with a patient of HS who was diagnosed clinically with only 10% spherical-shaped erythrocytes in the peripheral blood and received splenectomy. Sanger sequencing further confirmed that only the patient carried heterozygous ANK1 c.4276C>T nonsense mutation, while none of his parents or his young brother carried this mutation. Moreover, consistent with the genetic findings, the anemia was ameliorated after splenectomy. RBCs increased from 2.74 × 1012/L pre-surgery to 4.76 × 1012/L one month post-surgery, and hemoglobin increased from 66g/L to 126g/L respectively. This is the first report of ANK1 c.4276C>T (p.R1426*) heterozygous nonsense mutation responsible for HS. Our results also demonstrate that targeted NGS may provide a powerful approach for rapid genetic test of HS.
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