UNASSIGNED: Retrospective review of medical records, including cardiac investigations, was performed for families attending a specialized clinic with a FLNC truncating variant (FLNCtv). Variants were classified according to accepted variant interpretation criteria. Of seven families identified, six had primary cardiac phenotypes with one nonsense and five frameshift variants (nonsense-mediated decay competent) identified. One family had no cardiac phenotype, with a pathogenic variant (p.Arg2467Alafs*62) identified as secondary genetic finding. Of the six with cardiac phenotypes, proband age at diagnosis ranged 27-35 years (four females). Five families experienced sudden cardiac death (SCD) of a young relative (age range: 30-43 years), and one patient listed for cardiac transplant. Left ventricular (LV) ejection fraction ranged from 13 to 46%, with LV fibrosis (late gadolinium enhancement) on cardiac imaging or on postmortem histology seen in three families. Two families had one genotype-positive/phenotype-negative relative.
UNASSIGNED: The FLNCtv causes a left-sided ACM phenotype with a high risk of severe cardiac outcomes including end-stage heart failure and SCD. Incomplete penetrance is observed with implications for reporting secondary genetic findings.
■病历回顾性审查,包括心脏检查,为使用FLNC截断变体(FLNCtv)参加专门诊所的家庭进行。根据公认的变体解释标准对变体进行分类。在确定的七个家庭中,六个具有主要的心脏表型,其中一个无义和五个移码变体(无义介导的衰变能力)被鉴定。一个家族没有心脏表型,具有致病性变体(p。Arg2467Alafs*62)被鉴定为次要遗传发现。在六种有心脏表型的人中,诊断时的先证者年龄为27-35岁(4名女性).五个家庭经历了一个年轻亲戚的心脏猝死(SCD)(年龄范围:30-43岁),还有一名患者被列入心脏移植名单.左心室(LV)射血分数为13%至46%,在三个家庭中可见的心脏成像或死后组织学上的LV纤维化(晚钆增强)。两个家族有一个基因型阳性/表型阴性亲戚。
■FLNCtv导致左侧ACM表型,具有严重心脏后果的高风险,包括终末期心力衰竭和SCD。观察到不完整的外显率,对报告次要遗传发现有影响。