The distribution and frequency of the CFTR gene mutations vary considerably between countries and ethnic groups. Russians are an East Slavic ethnic groups are native to Eastern Europe. Russians, the most numerous people of the Russian Federation (RF), make about 80% of the population. The aim is to reveal the molecular causes of CF in ethnic Russian patients as comprehensively as possible. The analysis of most common CFTR mutations utilized for CF diagnosis in multiethnic RF population accounts for about 83% of all CF-causing mutations in 1384 ethnic Russian patients. Variants c.1521_1523delCTT (F508del), c.54-5940_273+10250del21kb (CFTRdele2,3), c.2012delT (2143delT), c.2052_2053insA (2184insA), and c.3691delT (3821delT) are most typical for CF patients of Russian origin. DNA of 154 CF patients, Russian by origin, in whom at least one mutant allele was not previously identified (164 CF alleles), was analyzed by Sanger sequencing followed by the multiplex ligase-dependent probe amplification (MLPA) method. In addition to the 29 variants identified during the previous test for common mutations, 91 pathogenic CFTR variants were also revealed: 29 missense, 19 nonsense, 14 frame shift in/del, 17 splicing, 1 in frame ins, and 11 copy number variations (CNV). Each of the 61 variants was revealed once, and 17 twice. Each of the variants c.1209G>C (E403D), c.2128A>T (K710X), c.3883delA (4015delA), and c.3884_3885insT (4016insT) were detected for three, c.1766+1G>A (1898+1G>A) and c.2834C>T (S945L) for four, c.1766+1G>C (1898+1G>C) and c.(743+1_744-1)_(1584+1_1585-1)dup (CFTRdup6b-10) for five, c.2353C>T (R785X) and c.4004T>C (L1335P) for six, c.3929G>A (W1310X) for seven, c.580-1G>T (712-1G>T for eight, and c.1240_1244delCAAAA (1365del5) for 11 unrelated patients. A comprehensive analysis of CFTR mutant alleles with sequencing followed by MLPA, allowed not only the identification of 163 of 164 unknown alleles in our patient sample, but also expansion of the mutation spectrum with novel and additional frequent variants for ethnic Russians.

中文翻译：

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俄罗斯族囊性纤维化患者CFTR突变谱分析

CFTR 基因突变的分布和频率在不同国家和种族群体之间差异很大。俄罗斯人属于东斯拉夫民族，原产于东欧。俄罗斯人是俄罗斯联邦 (RF) 人口最多的民族，约占总人口的 80%。目的是尽可能全面地揭示俄罗斯族患者 CF 的分子原因。对多种族 RF 人群中用于 CF 诊断的最常见 CFTR 突变的分析约占 1384 名俄罗斯族患者中所有 CF 引起突变的 83%。变体 c.1521_1523delCTT (F508del)、c.54-5940_273+10250del21kb (CFTRdele2,3)、c.2012delT (2143delT)、c.2052_2053insA (2184insA) 和 c.3691delT (3821delT) 对于 CF 患者来说是最典型的俄语起源。通过 Sanger 测序和多重连接酶依赖性探针扩增 (MLPA) 方法对 154 名俄罗斯裔 CF 患者的 DNA 进行了分析，其中至少有一个突变等位基因之前未被识别（164 个 CF 等位基因）。除了之前的常见突变测试中鉴定出的 29 个变异之外，还揭示了 91 个致病性 CFTR 变异：29 个错义、19 个无义、14 个移码/删除、17 个剪接、1 个移框插入和 11 个拷贝数变异（ CNV）。61 个变体中的每一个都被揭示了一次，17 个变体则被揭示了两次。检测到三个变体 c.1209G>C (E403D)、c.2128A>T (K710X)、c.3883delA (4015delA) 和 c.3884_3885insT (4016insT)，c.1766+1G>A (1898) +1G>A) 和 c.2834C>T (S945L) 为四个，c.1766+1G>C (1898+1G>C) 和 c.(743+1_744-1)_(1584+1_1585-1)dup (CFTRdup6b-10) 用于 5 个，c.2353C>T (R785X) 和 c.4004T>C (L1335P) 用于 6 个，c.3929G>A (W1310X) 用于 7 个，c.580-1G>T (712-1G) >T 代表 8 名，c.1240_1244delCAAAA (1365del5) 代表 11 名不相关的患者。对 CFTR 突变等位基因进行全面分析，并进行测序和 MLPA，不仅可以鉴定我们患者样本中 164 个未知等位基因中的 163 个，还可以扩展俄罗斯族人的突变谱具有新的和其他常见的变异。