Identification of a Novel Four and a Half LIM Domain 1 Mutation in a Chinese Male Presented with Hypertrophic Cardiomyopathy and Mild Skeletal Muscle Hypertrophy

Correspondence To the Editor: The human four and a half LIM domain 1 (FHL1) gene, located on Xq26.3, encodes for a protein with only LIM domains. LIM domains, named after their initial discovery in the proteins Lin11, Isl‑1, and Mec‑3, are cysteine‑rich protein motifs composed of two contiguous zinc finger domains separated by a two‑amino acid residue hydrophobic linker. At least three splice patterns have been identified, resulting in three protein isoforms: FHL1A with four and a half LIM repeats, FHL1B with three and a half repeats, and FHL1C with two and a half repeats. All isoforms are highly expressed in skeletal muscle and heart, where they are reported to play multiple roles in cell growth and function. Mutations of FHL1 gene could cause a series of diseases characterized by cardiac defects and/or skeletal muscle abnormalities. Recently, the FHL1 gene has been identified as one of the causative genes of hypertrophic cardiomyopathy (HCM). HCM is characterized by asymmetric left ventricular (LV) hypertrophy and diastolic dysfunction. The phenotype ranged from asymptomatic to dyspnea, heart failure, syncope, and sudden death. Here we report a Chinese male with HCM and mild skeletal muscle hypertrophy who was identified with a novel FHL1 mutation. A 19‑year‑old male was presented for intermittent weakness and exertional dyspnea during the past year. No chest pain, fatigue, syncope, or paralysis was reported. His parents were completely asymptomatic, with normal results of cardiovascular and neurological examinations. Both of his maternal grandmother's brothers had unexplained cardiac diseases in their 50s and died 5 years later. None of his other family relatives had cardiac or skeletal muscle diseases. On general examination, the patient was normotensive. Chest and heart auscultations were normal. Jugular vein was normal, and there was no peripheral edema. Neurologic examination revealed an athletic habitus with hypertrophy of all limb muscles, and a short neck. Other neurologic examinations were unremarkable. The 6‑min walk test was within normal range. Laboratory examination revealed increased serum creatine kinase (741 U/L, normal 18–198 U/L) with normal CK‑MB and cTnI. Screening for auto‑antibodies was negative. Electrocardiogram demonstrated sinus rhythm and tittered right axis. Echocardiography showed asymmetrical LV hypertrophy with a maximal wall thickness of 18 mm at mid‑septum. The LV outflow was normal. Left atrium was enlarged to 36 mm. Pulmonary systolic pressure was slightly raised to 46 mmHg. Magnetic resonance imaging of the heart demonstrated enlarged LV and right ventricle in a spiral pattern …