Novel Compound Heterozygous Missense Variants in RPL3L Gene Associated With Neonatal Dilated Cardiomyopathy

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology
• Rare Genetic Disorders

Background:

• Dilated cardiomyopathy type 2D (CMD2D) is a severe, early-onset genetic heart condition with high mortality.
• Mutations in RPL3L, a muscle-specific ribosomal protein gene, are known causes of CMD2D.
• The genetic and clinical spectrum of CMD2D remains incompletely understood, with limited reported cases.

Observation:

• Whole exome sequencing identified compound heterozygous RPL3L variants (c.346C>T and c.605A>G) in an infant with fulminant dilated cardiomyopathy.
• Histopathological examination revealed cardiomyocyte death, fibrosis, mitochondrial dysfunction, and sarcomeric disorganization.
• Protein modeling indicated these RPL3L mutations induce significant conformational changes.

Findings:

• This case expands the known mutational spectrum for RPL3L-related CMD2D.
• The identified variants (p.R116C and p.E202G) are associated with severe, neonatal-onset cardiomyopathy.
• The findings highlight the critical role of RPL3L in cardiac development and function.

Implications:

• Further genotype-phenotype correlations are crucial for understanding CMD2D pathogenesis.
• This research underscores the importance of genetic testing for RPL3L in infants with severe cardiomyopathy.
• Identifying novel mutations aids in developing diagnostic and potentially therapeutic strategies for rare cardiac disorders.