Hu Yunwen, Liu Guangzhong, Yuan Jie, Yin Da, Lin Yaowang
Department of Cardiology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), 1017 North Dongmen road, ShenZhen 518020, China.
Cardiovascular Minimally Invasive Medical Engineering Technology Research and Development Center, Shenzhen Key Medical Discipline (SZXK003), 1017 North Dongmen road, Shenzhen 518020, Guangdong, China.
Eur Heart J Case Rep. 2025 Apr 10;9(5):ytaf180. doi: 10.1093/ehjcr/ytaf180. eCollection 2025 May.
Genetic disorders are a significant cause of cardiomyopathies. Mutations in the gene (OMIM #604488) encoding the Z-disc protein Telethonin associated with a mixed phenotype of hypertrophic and restrictive cardiomyopathy with poor prognosis have not yet been reported.
A 47-year-old male presented with heart failure symptoms over a year, which had worsened in the past week. He has a familial history of cardiomyopathy, as his mother was diagnosed with restrictive cardiomyopathy (RCM). Transthoracic echocardiography and cardiac magnetic resonance imaging (CMR) revealed non-obstructive hypertrophic cardiomyopathy (HCM) with severe diastolic dysfunction, biatrial enlargement, preserved ejection fraction, and normal chamber size. Endomyocardial biopsy demonstrated cardiomyocyte hypertrophy and focal fibrosis. The patient was diagnosed with hypertrophic cardiomyopathy with a restrictive phenotype (RP-HCM). Whole exome sequencing identified a frameshift mutation producing a truncated product (p.Glu12fs) in the family. Despite interventions, the patient's cardiac function progressively deteriorated, leading to his placement on the heart transplant waiting list 1 year later.
In conclusion, we report for the first time that a heterozygous frameshift mutation resulting in a truncated protein product may contribute to the development of RP-HCM, providing new insights into the genetic basis of cardiomyopathy with mixed phenotypes.
遗传疾病是心肌病的重要病因。编码Z盘蛋白肌联蛋白（OMIM #604488）的基因突变与肥厚型和限制型心肌病的混合表型相关，预后较差，但尚未见报道。
一名47岁男性出现心力衰竭症状超过一年，在过去一周内病情加重。他有心肌病家族史，其母亲被诊断为限制型心肌病（RCM）。经胸超声心动图和心脏磁共振成像（CMR）显示为非梗阻性肥厚型心肌病（HCM），伴有严重舒张功能障碍、双房扩大、射血分数保留和心腔大小正常。心内膜心肌活检显示心肌细胞肥大和局灶性纤维化。该患者被诊断为具有限制型表型的肥厚型心肌病（RP-HCM）。全外显子组测序在该家族中发现了一个导致截短产物的移码突变（p.Glu12fs）。尽管进行了干预，患者的心功能仍逐渐恶化，1年后被列入心脏移植等待名单。
总之，我们首次报道杂合移码突变导致截短蛋白产物可能促成RP-HCM的发生，为具有混合表型的心肌病的遗传基础提供了新的见解。
