联合免疫缺陷病例中的纯合子RAG1基因突变:临床、分子和计算分析。

IF 1.1 4区生物学 Q4 GENETICS & HEREDITY Human Heredity Pub Date : 2019-01-01 Epub Date: 2020-10-19 DOI:10.1159/000510062

Soukaina Essadssi, Ibtihal Benhsaien, Amina Bakhchane, Hicham Charoute, Houria Abdelghaffar, Ahmed Aziz Bousfiha, Abdelhamid Barakat

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引用次数: 0

摘要

背景:重组激活基因1和2 (RAG1/RAG2)蛋白是启动V(D)J重组过程所必需的，其结果是抗原受体基因的多样化和适应性免疫的建立。RAG1突变可导致多种形式的联合免疫缺陷。方法:在本报告中，对一名患有合并免疫缺陷、T淋巴细胞和B淋巴细胞减少症、自身免疫性溶血性贫血和巨细胞病毒(CMV)感染的摩洛哥儿童进行了全外显子组测序。结果:经数据筛选和Sanger测序验证，在RAG1基因中鉴定出一个纯合突变c.2446G>A (p.Gly816Arg)。结论:这一发现扩大了与RAG1突变相关的免疫学和遗传学谱，它也说明了在自身免疫性溶血性贫血和巨细胞病毒感染存在时考虑RAG1免疫缺陷的必要性，即使假设免疫表型或多或少正常。

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A Homozygous RAG1 Gene Mutation in a Case of Combined Immunodeficiency: Clinical, Molecular, and Computational Analysis.

Background: The recombination-activating gene 1 and 2 (RAG1/RAG2) proteins are essential to initiate the V(D)J recombination process, the result is a diverse repertoire of antigen receptor genes and the establishment of the adaptive immunity. RAG1 mutations can lead to multiple forms of combined immunodeficiency.

Methods: In this report, whole exome sequencing was performed in a Moroccan child suffering from combined immunodeficiency, with T and B lymphopenia, autoimmune hemolytic anemia, and cytomegalovirus (CMV) infection.

Results: After filtering data and Sanger sequencing validation, one homozygous mutation c.2446G>A (p.Gly816Arg) was identified in the RAG1 gene.

Conclusion: This finding expands the spectrum of immunological and genetic profiles linked to RAG1 mutation, it also illustrates the necessity to consider RAG1 immunodeficiency in the presence of autoimmune hemolytic anemia and CMV infection, even assuming the immunological phenotype appears more or less normal.

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来源期刊

Human Heredity 生物-遗传学

CiteScore

2.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Gathering original research reports and short communications from all over the world, ''Human Heredity'' is devoted to methodological and applied research on the genetics of human populations, association and linkage analysis, genetic mechanisms of disease, and new methods for statistical genetics, for example, analysis of rare variants and results from next generation sequencing. The value of this information to many branches of medicine is shown by the number of citations the journal receives in fields ranging from immunology and hematology to epidemiology and public health planning, and the fact that at least 50% of all ''Human Heredity'' papers are still cited more than 8 years after publication (according to ISI Journal Citation Reports). Special issues on methodological topics (such as ‘Consanguinity and Genomics’ in 2014; ‘Analyzing Rare Variants in Complex Diseases’ in 2012) or reviews of advances in particular fields (‘Genetic Diversity in European Populations: Evolutionary Evidence and Medical Implications’ in 2014; ‘Genes and the Environment in Obesity’ in 2013) are published every year. Renowned experts in the field are invited to contribute to these special issues.