Novel compound heterozygous variants in the RPL3L gene causing dilated cardiomyopathy type-2D: a case report and literature review

Background Dilated cardiomyopathy type-2D (CMD2D) is a rare heart disease causing a severe cardiomyopathy with neonatal onset and rapid progression to cardiac decompensation and death in untreated patients. CMD2D is an autosomal recessive disease resulting from variants in the RPL3L gene, which encodes the 60 S ribosomal protein exclusively expressed in skeletal and cardiac muscle and plays an essential role in myoblast growth and fusion. Previous reports have only associated CMD2D with a small duplication and seven nucleotide substitution in the RPL3L gene. Case presentation In this study, we report the case of a 31 days old Chinese infant patient with severe dilated cardiomyopathy (DCM) and rapid decompensation along with other cardiac malformations. In addition to previously reported clinical features, the patient showed the previously unreported complication of occasional premature atrial contractions and a first-degree atrioventricular block. Whole-exome sequencing (WES) revealed compound heterozygous variants (c.80G > A (p.Gly27Asp) and c.1074dupA (p.Ala359fs*6)) in RPL3L (NM_005061.3). The latter novel variant may result in the absence of protein production with a significant decrease in mRNA level, suggesting it is a loss-of-function mutation. Conclusions This is the first case report of RPL3L -associated neonatal dilated cardiomyopathy in China. The molecular confirmation of the patient expands the genetic spectrum of CMD2D, and the clinical manifestation of CMD2D in the patient provides additional clinical information regarding this disease.