Abstract：
The singular BRCA1/2 mutational landscape of Asturias is updated 10 years after the first study. We analyzed BRCA1 and BRCA2 pathogenic variants in 1653 index cases. In total, 238 families were identified to carry a pathogenic variant, 163 families in BRCA1 and 75 families in BRCA2. This yielded a prevalence rate of 14.4%. Seven recurrent variants were found accounting for 55% of the cases. Among them, three are widely distributed (BRCA1 c.211A>G, c.470_471del and c.3331_3334del) and four had been reported as novel in Asturias: two in BRCA1 (c.1674del and c.2901_2902dup) and two in BRCA2 (c.2095C>T and c.4040_4035delinsC). A common haplotype was established for all recurrent variants indicating a shared ancestral origin. Three splicing analyses are shown: BRCA1:c.5152+3A>C and BRCA1:c.5333-3T>G that lead to skipping of exon 18, and 22 respectively, and BRCA1:c.5278-1G>T giving rise to two transcripts, one lacking exon 21 (p.Ille1760Glyfs*60) and one lacking the first 8 nucleotides of exon 21 (p.Phe1761Asnfs*14), supporting pathogenicity for these variants.
摘要：
阿斯图里亚斯的奇异BRCA1/2突变景观在第一项研究后10年更新。我们分析了1653个指标病例中的BRCA1和BRCA2致病变异。总的来说,238个家族被确定携带致病变异，BRCA1的163个家庭和BRCA2的75个家庭。这产生了14.4%的患病率。发现了七个复发性变异，占病例的55％。其中,三个分布广泛(BRCA1c.21A>G，c.470_471del和c.3331_3334del）和四个在阿斯图里亚斯被报道为新颖：两个在BRCA1中（c.1674del和c.2901_2902dup）和两个在BRCA2中（c.2095C>T和c.4040_4035delinsC）。为所有复发性变体建立了共同的单倍型，表明共有的祖先起源。显示了三个剪接分析：BRCA1：c.51523A>C和BRCA1：c.5333-3T>G，分别导致外显子18和22的跳过，和BRCA1：c.5278-1G>T产生两个转录本，一个缺少外显子21（第Ille1760Glyfs*60）和一个缺少外显子21的前8个核苷酸（p。Phe1761Asnfs*14)，支持这些变体的致病性。
