Identification of novel variants in hereditary spherocytosis patients by whole-exome sequencing.

IF 3.2 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2024-10-06 DOI:10.1016/j.cca.2024.119989

Li Qin, Yujiao Jia, Haoxu Wang, Yuan Feng, Junyan Zou, Jianfeng Zhou, Changshun Yu, Bingqing Huang, Ruixue Zhang, Lihui Shi, Jigang Xiao, Yuping Zhao, Qi Sun, Zhijian Xiao, Huijun Wang

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Abstract

Defects in erythrocyte membrane proteins can cause the most common type of inherited hemolytic anemia, so called hereditary spherocytosis (HS). It is characterized by the appearance of spherocytes in peripheral blood, hemolytic anemia, splenomegaly, jaundice and gallstones. Due to difficulty of diagnosis solely based on aforementioned parameters, the addition of genetic testing seems to be effective and most acknowledged. Up to date, pathogenic variations in five genes encoding membrane proteins (ANK1, SPTA1, SPTB, SLC4A1, EPB42) are identified to cause HS. Here, we have studied the genetic spectrum in forty-one patients with clinically suspected HS and their families, as well as their genotype-phenotype correlations. Pathogenic mutations in ANK1, SPTB, SLC4A1 and SPTA1 were found in 17 (41.5 %), 12 (29.3 %), 7 (17.1 %) and 5 (12.2 %) patients, respectively. Deleterious variants include 12 missense, 15 nonsense, 12 frameshift, and 4 splicing variants. Among these variations 32 were novel. In our genotype-phenotype analysis, platelet levels in SPTB (p = 0.021) and SLC4A1 (p = 0.02) patients were found to be significantly lower than ANK1 patients. In addition, LDH levels in SPTB patients were remarkably lower than patients with ANK1 mutations (p = 0.025).

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通过全外显子组测序鉴定遗传性球形红细胞增多症患者的新型突变。

红细胞膜蛋白质缺陷可导致最常见的遗传性溶血性贫血，即遗传性球形红细胞增多症（HS）。其特征是外周血中出现球形细胞、溶血性贫血、脾肿大、黄疸和胆结石。由于仅根据上述参数难以确诊，增加基因检测似乎是最有效和最被认可的方法。迄今为止，已发现五个编码膜蛋白的基因（ANK1、SPTA1、SPTB、SLC4A1、EPB42）的致病变异可导致 HS。在此，我们研究了 41 例临床疑似 HS 患者及其家族的基因谱，以及他们的基因型与表型之间的相关性。在 17 例（41.5%）、12 例（29.3%）、7 例（17.1%）和 5 例（12.2%）患者中分别发现了 ANK1、SPTB、SLC4A1 和 SPTA1 的致病突变。致畸变异包括 12 个错义变异、15 个无义变异、12 个框移变异和 4 个剪接变异。这些变异中有 32 个是新变异。在我们的基因型-表型分析中，发现 SPTB（p = 0.021）和 SLC4A1（p = 0.02）患者的血小板水平明显低于 ANK1 患者。此外，SPTB 患者的 LDH 水平明显低于 ANK1 突变患者（p = 0.025）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.