Abstract：
More than 450 genetic defects result in inborn errors of immunity (IEI). Their individual prevalence in specific cohorts is influenced by national characteristics and other factors. We present results of genetic testing conducted in 1809 Russian children with IEI. Genetic defects confirming IEI were found in 1112 out of 1809 (61.5%) probands. These defects included variants in 118 single genes (87.9% of patients) and aberrations in 6 chromosomes (11.8%). Notably, three patients harbored pathogenic variants in more than one IEI gene. Large deletions constituted 5% of all defects. Out of the 799 original variants, 350 (44%) have not been described previously. Rare genetic defects (10 or fewer patients per gene) were identified in 20% of the patients. Among 967 probands with germline variants, defects were inherited in an autosomal dominant manner in 29%, X-linked in 34%, and autosomal recessive in 37%. Four females with non-random X-inactivation exhibited symptoms of X-linked diseases (BTK, WAS, CYBB, IKBKG gene defects). Despite a relatively low rate of consanguinity in Russia, 47.9% of autosomal recessive gene defects were found in a homozygous state. Notably, 28% of these cases carried \"Slavic\" mutation of the NBN gene or known hot-spot mutations in other genes. The diversity of IEI genetic forms and the high frequency of newly described variants underscore the genetic heterogeneity within the Russian IEI group. The new variants identified in this extensive cohort will enrich genetic databases.
摘要：
超过450个基因缺陷导致先天免疫错误（IEI）。他们在特定人群中的个体患病率受到民族特征和其他因素的影响。我们介绍了1809年俄罗斯IEI儿童的基因检测结果。在1809个先证者中的1112个（61.5％）中发现了确认IEI的遗传缺陷。这些缺陷包括118个单个基因的变异（87.9％的患者）和6个染色体的畸变（11.8％）。值得注意的是,3名患者在一个以上的IEI基因中携带致病变异。大的缺失占所有缺陷的5%。在799个原始变体中，350（44％）以前没有描述过。在20％的患者中发现了罕见的遗传缺陷（每个基因10名或更少的患者）。在967个有种系变异的先证者中，29%的缺陷以常染色体显性遗传，34%的X连接，37%的常染色体隐性遗传。四名非随机X失活的女性表现出X连锁疾病的症状(BTK，WAS,CYBB,IKBKG基因缺陷）。尽管俄罗斯的血缘率相对较低，47.9％的常染色体隐性基因缺陷处于纯合状态。值得注意的是,这些病例中有28％携带NBN基因的“斯拉夫”突变或其他基因中已知的热点突变。IEI遗传形式的多样性和新描述的变异的高频率强调了俄罗斯IEI群体内的遗传异质性。在这个广泛的队列中发现的新变体将丰富遗传数据库。
