Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7.
Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: New Variant p.Arg652Lys in MYH7.
复制标题
DOI：
10.3390/genes13020320
复制
发表时间：
2022-02-09
期刊：
影响因子：
3.5
通讯作者：
Ripoll-Vera T
中科院分区：
文献类型：
--
作者：
Antoniutti G;Caimi-Martinez FG;Álvarez-Rubio J;Morlanes-Gracia P;Pons-Llinares J;Rodríguez-Picón B;Fortuny-Frau E;Torres-Juan L;Heine-Suner D;Ripoll-Vera T
肥厚型心肌病（HCM）是一种遗传性疾病，其特征是由肌节基因突变引起的左心室（LV）壁厚度增加。找到一个因果突变可以帮助更好地评估先证者的风险，因为它允许在亲属中评估突变的存在，并将后续工作集中在携带者身上。我们对MYH7基因中新的p.Arg652Lys变异导致的HCM患者进行了一项观察性研究。8个家庭和59例患者的中位随访时间为63个月，其中39例（66%）携带变异。25名（64%）携带者发展为HCM。左心室壁最大厚度中位数为16.5 mm。75%的左室肥厚表现为不对称性室间隔肥厚，28%的左室流出道梗阻。在5例（20%）患者中观察到严重不良心血管事件复合事件（猝死、流产猝死、适当的植入式心脏除颤器放电、栓塞事件或因心力衰竭入院）的发生率。鉴于p.Arg652Lys变异在HCM患者中的发现，而不是在对照组中，HCM患者明显分离于8个家族，并且位于蛋白质的活性位点，我们可以将该变异定义为可能的致病性并与HCM的发展相关。
Hypertrophic cardiomyopathy (HCM) is a genetic disease characterised by increased left ventricle (LV) wall thickness caused by mutations in sarcomeric genes. Finding a causal mutation can help to better assess the proband’s risk, as it allows the presence of the mutation to be evaluated in relatives and the follow-up to be focused on carriers. We performed an observational study of patients with HCM due to the novel p.Arg652Lys variant in the MYH7 gene. Eight families and 59 patients are described in the follow-up for a median of 63 months, among whom 39 (66%) carry the variant. Twenty-five (64%) of carriers developed HCM. A median maximum LV wall thickness of 16.5 mm was described. The LV hypertrophy was asymmetric septal in 75% of cases, with LV outflow tract obstruction in 28%. The incidence of a composite of serious adverse cardiovascular events (sudden death, aborted sudden death, appropriate implantable cardiac defibrillator discharge, an embolic event, or admission for heart failure) was observed in five (20%) patients. Given the finding of the p.Arg652Lys variant in patients with HCM, but not in controls, with evident segregation in patients with HCM from eight families and the location in an active site of the protein, we can define this variant as likely pathogenic and associated with the development of HCM.
登录
查看更多内容
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：
64.5
作者：
GEISTERFERLOWRANCE, AAT;KASS, S;SEIDMAN, JG
通讯作者：
SEIDMAN, JG
影响因子：
5.7
作者：
Ingles, Jodie;McGaughran, Julie;Semsarian, Christopher
通讯作者：
Semsarian, Christopher
影响因子：
37.8
作者：
Ho, CY;Sweitzer, NK;Solomon, SD
通讯作者：
Solomon, SD
影响因子：
6.2
作者：
Sen-Chowdhry, Srijita;McKenna, William J.
通讯作者：
McKenna, William J.