Clinical characteristics and genetic profiles of 174 patients with X-linked agammaglobulinemia: Report from Shanghai, China (2000-2015).
Clinical characteristics and genetic profiles of 174 patients with X-linked agammaglobulinemia: Report from Shanghai, China (2000-2015).
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中国上海174例X连锁无丙种球蛋白血症患者的临床特征和基因谱报告（2000-2015年）
DOI：
10.1097/md.0000000000004544
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发表时间：
2016-08
期刊：
影响因子：
1.6
通讯作者：
Chen TX
中科院分区：
文献类型：
--
作者：
Chen XF;Wang WF;Zhang YD;Zhao W;Wu J;Chen TX
X连锁无丙种球蛋白血症(XLA)是一种体液原发免疫缺陷。XLA患者的外周B细胞数量非常少，所有免疫球蛋白同型都严重缺乏。大多数XLA患者携带Bruton酪氨酸激酶(BTK)基因突变。本文对174例中国人XLA的遗传背景和临床特征进行了研究。本研究还探讨了BTK基因突变与临床表现严重程度的关系。通过生物信息学分析，根据结构和功能预测，将突变从轻微到严重分级。在12 4个家系的14 2名患者中发现了127个突变，其中包括45个新突变和82个重复突变，分布在整个BTK基因序列上。观察到表型的变化，并且在基因和发病年龄之间有关联的趋势。这份报告构成了中国BTK突变患者中最大的群体。在本研究中观察到了基因-表型的相关性。先天性无丙种球蛋白血症的早期诊断应基于临床症状、家族史和BTK基因的分子分析。
X-linked agammaglobulinemia (XLA) is a humoral primary immunodeficiency. XLA patients typically present with very low numbers of peripheral B cells and a profound deficiency of all immunoglobulin isotypes. Most XLA patients carry mutations in Bruton tyrosine kinase (BTK) gene. The genetic background and clinical features of 174 Chinese patients with XLA were investigated. The relationship between specific BTK gene mutations and severity of clinical manifestations was also examined. Mutations were graded from mild to severe based on structural and functional prediction through bioinformatics analysis. One hundred twenty-seven mutations were identified in 142 patients from 124 families, including 45 novel mutations and 82 recurrent mutations that were distributed over the entire BTK gene sequence. Variation in phenotypes was observed, and there was a tendency of association between genotype and age of disease onset. This report constitutes the largest group of patients with BTK mutations in China. A genotype–phenotype correlation was observed in this study. Early diagnosis of congenital agammaglobulinemia should be based on clinical symptoms, family history, and molecular analysis of the BTK gene.