Department of Cell Biology, The School of Life Sciences, Central South University, Changsha, China.
Department of Nephrology, The Third Xiangya Hospital of Central South University, Changsha, China.
J Gene Med. 2019 Feb;21(2-3):e3073. doi: 10.1002/jgm.3073. Epub 2019 Feb 11.
Hereditary 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.
In 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.
After 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 β-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.
The 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.
遗传性球形红细胞增多症（HS）是一种遗传性红细胞疾病。HS 的典型特征是外周血涂片上存在球形红细胞。根据以往的研究，已经在 HS 患者中鉴定出超过五个候选基因，如 ANK1、SPTB、SPTA1、SLC4A1 和 EPB42。
本研究调查了一个中国 HS 家族。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。
经过数据过滤和共分离分析，我们在受影响的成员中发现了 12 个突变，而在健康成员中则没有。考虑到遗传模式、在线孟德尔遗传人类临床表型、Toppgene 功能和美国医学遗传学分类，我们认为β- spectrin（SPTB）的新突变（c.5650G>C/p.Ala1884Pro）是该家族的遗传病变。该新突变导致丙氨酸被脯氨酸取代，可能导致 SPTB 蛋白结构的改变，从而影响 SPTB 和锚蛋白之间的结合。
本研究从分子水平证实了遗传性红细胞膜疾病，并扩展了 SPTB 突变谱。这可能有助于 HS 的临床管理和遗传咨询。
