Department of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.
Laboratory of Molecular Biology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.
J Clin Immunol. 2024 Jul 25;44(7):165. doi: 10.1007/s10875-024-01767-w.
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.
超过 450 种遗传缺陷可导致先天性免疫缺陷（IEI）。它们在特定队列中的个体患病率受到国家特征和其他因素的影响。我们报告了在 1809 名俄罗斯 IEI 患儿中进行的基因检测结果。在 1809 名先证者中，有 1112 名（61.5%）发现了明确的 IEI 遗传缺陷。这些缺陷包括 118 个单一基因中的变异（87.9%的患者）和 6 条染色体的异常（11.8%）。值得注意的是，有 3 名患者携带了一种以上 IEI 基因的致病性变异。大片段缺失占所有缺陷的 5%。在 799 个原始变异中，有 350 个（44%）以前未被描述过。在 20%的患者中发现了罕见的遗传缺陷（每个基因 10 个或更少的患者）。在 967 名具有种系变异的先证者中，缺陷以常染色体显性方式遗传的占 29%，X 连锁遗传的占 34%，常染色体隐性遗传的占 37%。4 名非随机 X 染色体失活的女性表现出 X 连锁疾病的症状（BTK、WAS、CYBB、IKBKG 基因缺陷）。尽管俄罗斯的近亲结婚率相对较低，但 47.9%的常染色体隐性基因缺陷为纯合状态。值得注意的是，这些病例中有 28%携带 NBN 基因的“斯拉夫”突变或其他基因的热点突变。IEI 遗传形式的多样性和新描述变异的高频度突出了俄罗斯 IEI 群体的遗传异质性。在这个广泛的队列中发现的新变异将丰富遗传数据库。
