Prevalence and Phenotypic Expression of Mutations in the MYH7, MYBPC3 and TNNT2 Genes in Families with Hypertrophic Cardiomyopathy in the South of Brazil: A Cross-Sectional Study.
Prevalence and Phenotypic Expression of Mutations in the MYH7, MYBPC3 and TNNT2 Genes in Families with Hypertrophic Cardiomyopathy in the South of Brazil: A Cross-Sectional Study.
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DOI：
10.5935/abc.20160133
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发表时间：
2016-09
影响因子：
2.6
通讯作者：
Matte Ú
中科院分区：
文献类型：
--
作者：
Mattos BP;Scolari FL;Torres MA;Simon L;Freitas VC;Giugliani R;Matte Ú
60-70% 患有家族性肥厚型心肌病 (HCM) 的个体存在肌节基因突变。然而，这一估计是针对北半球的人口。在巴西，特别是在该国南部，HCM 的分子遗传学特征很少受到调查。研究居住在巴西最南端的一群 HCM 患者的肌节基因 MYH7、MYBPC3 和 TNNT2 的突变，并评估基因型与表型的关联。对 10 个不相关家族的 43 个连续个体进行了三个肌节基因所有编码区的直接 DNA 测序。在 10 个研究家庭中的 7 个 (70%) 家庭中，有 25 名 (58%) 患者发现了 CMH 突变。十四 (56%) 个体呈表型阳性。所有突变均为错义，其中 4 个 (66%) 发生在 MYH7 中，2 个 (33%) 发生在 MYBPC3 中。我们尚未发现 TNNT2 基因突变。在 6 个 (60%) 个家庭的 20 名 (47%) 名患者中发现了 MYH7 突变。其中两个之前没有被描述过。两个 (20%) 个家庭的七名 (16%) 成员中发现了 MYBPC3 突变。两名（5%）患者表现出两个基因的双杂合性。这些突变影响编码蛋白质的不同域并导致表型表达的变化。所有基因型阳性个体均发现 HCM 家族史。在巴西南部进行的首次遗传分子分析中，我们发现 58% 的个体的肌节基因 MYH7 和 MYBPC3 存在突变。大多数 MYH7 相关疾病均存在突变。
Mutations in sarcomeric genes are found in 60-70% of individuals with familial forms of hypertrophic cardiomyopathy (HCM). However, this estimate refers to northern hemisphere populations. The molecular-genetic profile of HCM has been subject of few investigations in Brazil, particularly in the south of the country. To investigate mutations in the sarcomeric genes MYH7, MYBPC3 and TNNT2 in a cohort of HCM patients living in the extreme south of Brazil, and to evaluate genotype-phenotype associations. Direct DNA sequencing of all encoding regions of three sarcomeric genes was conducted in 43 consecutive individuals of ten unrelated families. Mutations for CMH have been found in 25 (58%) patients of seven (70%) of the ten study families. Fourteen (56%) individuals were phenotype-positive. All mutations were missense, four (66%) in MYH7 and two (33%) in MYBPC3. We have not found mutations in the TNNT2 gene. Mutations in MYH7 were identified in 20 (47%) patients of six (60%) families. Two of them had not been previously described. Mutations in MYBPC3 were found in seven (16%) members of two (20%) families. Two (5%) patients showed double heterozygosis for both genes. The mutations affected different domains of encoded proteins and led to variable phenotypic expression. A family history of HCM was identified in all genotype-positive individuals. In this first genetic-molecular analysis carried out in the south of Brazil, we found mutations in the sarcomeric genes MYH7 and MYBPC3 in 58% of individuals. MYH7-related disease was identified in the majority of cases with mutation.
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影响因子：
39.3
作者：
Elliott, Perry M.;Anastasakis, Aris;Watkins, Hugh
通讯作者：
Watkins, Hugh
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
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10.8
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作者：
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影响因子：
37.8
作者：
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通讯作者：
Yancy, Clyde W.