Hypertrophic cardiomyopathy associate with a PLN gene mutation in a child: a case report

Hypertrophic cardiomyopathy (HCM) is a common hereditary disease of the myocardium, caused by mutations in at least 20 genes, encoding cardiac sarcomere proteins and sarcomere-associated proteins, while genes related to calcium metabolism, such as phospholamban (PLN), have been reported rarely, in less than 1% of positive patients. This study aims to report a unique case of child's HCM caused by a missense variant in the PLN gene on chromosome 6 (NM_002667.5:c.106T>C, p.Cys36Arg). This mutation in children, not previously reported in the literature except for an adult, expand the known spectrum of PLN-related HCM and highlight the importance of comprehensive diagnostic approaches in children patients.

A 13-year-old male patient was admitted to the hospital due to "skin pallor", and was diagnosed with mild thalassemia by cytopenia and loss of heterozygosity of thalassemia gene α3.7. The symptoms were improved after iron supplementation. During hospitalization, the child complained of precordial pain. Echocardiogram and cardiac magnetic resonance (CMR) were performed, which showed thickening of the anterior septal basal segment, with the maximum thickness of 14 mm and a Z-score of 5.6 (Boston standard), and left ventricular outflow tract obstruction (dynamic). The subject carried a missense mutation of PLN gene on chromosome 6 detected by whole exon sequencing. The mutation was NM_002667.5:c.106T>C (p.Cys36Arg), heterozygous mutation, and the mutation was verified to be derived from the father. After the diagnosis was confirmed, the patient was given captopril, metoprolol and other drugs, and the chest pain was improved. A literature search revealed that this PLN gene variant site associated with HCM was reported only in an adult female, and this is the first case reported in a pediatric patient.

This case highlights HCM caused by PLN gene mutations, emphasizing the importance of comprehensive diagnostic workup in child patient with thickening of ventricular septum diseases. Additionally, it underscores the importance of genetic testing via whole-exome sequencing use and cardiac function care in HCM diseases.