Laboratorio de Genética Molecular Humana B, Departamento de Biología Celular, Universidad Simón Bolívar, Caracas, Venezuela.
Biol Res. 2012;45(2):117-30. doi: 10.4067/S0716-97602012000200003.
A sample of 58 familial breast cancer patients from Venezuela were screened for germline mutations in the coding sequences and exon-intron boundaries of BRCA1 (MIM no. 113705) and BRCA2 (MIM no. 600185) genes by using conformation-sensitive gel electrophoresis. Ashkenazi Jewish founder mutations were not found in any of the samples. We identified 6 (10.3%) and 4 (6.9%) patients carrying germline mutations in BRCA1 and BRCA2, respectively. Four pathogenic mutations were found in BRCA1, one is a novel mutation (c.951_952insA), while the other three had been previously reported (c.1129_1135insA, c.4603G>T and IVS20+1G>A). We also found 4 pathogenic mutations in BRCA2, two novel mutations (c.2732_2733insA and c.3870_3873delG) and two that have been already reported (c.3036_3039delACAA and c.6024_6025_delTA). In addition, 17 variants of unknown significance (6 BRCA1 variants and 11 BRCA2 variants), 5 BRCA2 variants with no clinical importance and 22 polymorphisms (12 in BRCA1 and 10 in BRCA2) were also identified. This is the first genetic study on BRCA gene mutations conducted in breast cancer patients from Venezuela. The ethnicity of our population, as well as the heterogeneous and broad spectrum of BRCA genes mutations, must be considered to optimize genetic counseling and disease prevention in affected families.
从委内瑞拉的 58 个家族性乳腺癌患者中抽取样本，通过构象敏感凝胶电泳法对 BRCA1（MIM 编号：113705）和 BRCA2（MIM 编号：600185）基因的编码序列和外显子-内含子边界进行种系突变筛查。在任何样本中均未发现阿什肯纳兹犹太裔的突变。我们分别在 BRCA1 和 BRCA2 中发现了 6（10.3%）和 4（6.9%）名患者存在种系突变。在 BRCA1 中发现了 4 种致病性突变，其中 1 种是新突变（c.951_952insA），另外 3 种之前已有报道（c.1129_1135insA、c.4603G>T 和 IVS20+1G>A）。在 BRCA2 中，我们还发现了 4 种致病性突变，其中 2 种是新突变（c.2732_2733insA 和 c.3870_3873delG），另外 2 种已有报道（c.3036_3039delACAA 和 c.6024_6025_delTA）。此外，还鉴定出了 17 种意义不明的变异（6 种 BRCA1 变异和 11 种 BRCA2 变异）、5 种无临床意义的 BRCA2 变异和 22 种多态性（BRCA1 中有 12 种，BRCA2 中有 10 种）。这是委内瑞拉乳腺癌患者中进行的首次 BRCA 基因突变的遗传研究。我们的人群种族以及 BRCA 基因突变的异质性和广泛谱型，必须加以考虑，以优化受影响家族的遗传咨询和疾病预防。
