Whole exome sequencing identified a novel mutation (p.Ala1884Pro) of -spectrin in a Chinese family with hereditary spherocytosis
Whole exome sequencing identified a novel mutation (p.Ala1884Pro) of -spectrin in a Chinese family with hereditary spherocytosis
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全外显子组测序在中国遗传性球形红细胞增多症家系中发现了β血影蛋白的新突变（p.Ala1884Pro）
DOI：
10.1002/jgm.3073
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发表时间：
2019-02-01
影响因子：
3.5
通讯作者：
Xiang, Rong
中科院分区：
文献类型：
--
作者：
Fan, Liang-Liang;Liu, Ji-Shi;Xiang, Rong
背景遗传性球形红细胞增多症（HS）是一种红细胞遗传性疾病。 HS的典型特征是外周血涂片上出现球形红细胞。根据既往研究，在HS患者中已鉴定出ANK1、SPTB、SPTA1、SLC4A1和EPB42等5个以上候选基因。方法本研究以一个中国HS家系为调查对象。先证者患有病理性黄疸和脾肿大。血液检查和外周血涂片实验进一步证实了HS的诊断。我们选择先证者进行全外显子组测序。结果经过数据过滤和共分离分析，我们在受影响的成员中鉴定出了健康成员中不存在的12个突变。综合考虑遗传模式、在线孟德尔遗传人类临床表型、Toppgene功能和美国医学遗传学学会分类，我们认为血影蛋白（SPTB）的新突变（c.5650G>C/p.Ala1884Pro）是该家系的遗传病变。这种新的突变导致丙氨酸被脯氨酸取代，可能导致SPTB蛋白结构的转变，从而影响SPTB和锚蛋白之间的结合。结论本研究在分子水平上证实了遗传性红细胞膜疾病，并扩大了SPTB突变谱。这可能有助于 HS 的临床管理和遗传咨询。
BackgroundHereditary spherocytosis (HS) is an inherited disorder of erythrocyte. The typical feature of HS is the presence of spherical-shaped erythrocytes on the peripheral blood smear. According to previous studies, more than five candidate genes, such as ANK1, SPTB, SPTA1, SLC4A1 and EPB42 have been identified in HS patients.MethodsIn the present study, a Chinese HS family was investigated. The proband suffered from pathologic jaundice and splenomegaly. A blood test and peripheral blood smear experiment further confirmed the diagnosis of HS. We selected the proband to perform the whole exome sequencing.ResultsAfter data filtering and co-segregation analysis, we identified 12 mutations in affected members that were absent in healthy members. In consideration of the inheritance pattern, Online Mendelian Inheritance in Man clinical phenotypes, Toppgene function and American College of Medical Genetics classification, we considered the novel mutation (c.5650G>C/p.Ala1884Pro) of -spectrin (SPTB) to be the genetic lesion in this family. The novel mutation, resulting in a substitution of alanine by proline, may lead to transformation of the SPTB protein structure, which affects the binding between SPTB and ankyrin.ConclusionsThe present study confirmed the hereditary red blood cell membrane disorders at a molecular level and expanded the spectrum of SPTB mutations. This may contribute to the clinical management and genetic counseling with respect to HS.