Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis
Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis
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DOI：
10.1111/cge.12749
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发表时间：
2016-07-01
影响因子：
3.5
通讯作者：
Kim, Y.
中科院分区：
文献类型：
--
作者：
Park, J.;Jeong, D-C.;Kim, Y.
本研究的目的是描述韩国遗传性球形红细胞增多症（HS）患者的突变特征。本文还回顾了相关文献，包括遗传确诊病例，并记录了充分的临床摘要和相关信息，以探讨突变基因或特定领域的实验室和临床关联。25例HS患者携带ANK1 （n = 13）或SPTB （n = 12）的杂合突变，但不携带SPTA1、SLC4A1或EPB42。91%（21/23）的有害突变包括移码突变、无义突变和剪接位点突变，非热点突变分散在多个外显子上。结合病例分析和文献复习，明确基因型与表型的相关性；HS患者在ANK1谱蛋白结合结构域发生突变时贫血最为严重（p < 0.05），而HS患者的SPTB突变保留了遗传性椭圆型细胞增多症和嗜热型细胞增多症突变所在的四聚体结构域。脾切除术（17/75）在ANK1突变HS（32%）中比在SPTB突变HS（10%）中更常见（p = 0.028）。32.0%（8/25, 3例ANK1, 5例SPTB）发生再生危象，88%检出细小病毒B19。本研究阐明了韩国HS患者的ANK1或SPTB突变特征。实验室和临床方面的遗传关联建议对HS的遗传管理进行综合考虑。
The aim of this study was to describe the mutational characteristics in Korean hereditary spherocytosis (HS) patients. Relevant literatures including genetically confirmed cases with well-documented clinical summaries and relevant information were also reviewed to investigate the mutational gene- or domain-specific laboratory and clinical association. Twenty-five HS patients carried one heterozygous mutation of ANK1 (n = 13) or SPTB (n = 12) but not in SPTA1, SLC4A1, or EPB42. Deleterious mutations including frameshift, nonsense, and splice site mutations were identified in 91% (21/23), and non-hotspot mutations were dispersed across multiple exons. Genotype-phenotype correlation was clarified after combined analysis of the cases and the literature review; anemia was most severe in HS patients with mutations on the ANK1 spectrin-binding domain (p < 0.05), and SPTB mutations in HS patients spared the tetramerization domain in which mutations of hereditary elliptocytosis and pyropoikilocytosis are located. Splenectomy (17/75) was more frequent in ANK1 mutant HS (32%) than in HS with SPTB mutation (10%) (p = 0.028). Aplastic crisis occurred in 32.0% of the patients (8/25; 3 ANK1 and 5 SPTB), and parvovirus B19 was detected in 88%. The study clarifies ANK1 or SPTB mutational characteristics in HS Korean patients. The genetic association of laboratory and clinical aspects suggests comprehensive considerations for genetic-based management of HS.