MEF2C Mutation Analysis in Patients with Congenital Heart Diseases Among the Tanzanian Population

Abstract

Background: Congenital heart disease (CHD) is the most common congenital anomaly worldwide and a leading cause of infant morbidity and mortality, particularly in low- and middle-income countries. Genetic factors, including mutations in cardiac transcription factor genes such as MEF2C, play a critical role in cardiac development. However, data on MEF2C gene mutations in Sub-Saharan Africa remain limited. This study aimed to determine the presence of MEF2C gene mutations among infants with CHD attending Jakaya Kikwete Cardiac Institute (JKCI), Tanzania.
Methods: A case-control study was conducted involving 62 infants with echocardiographically confirmed CHD and 101 healthy controls aged 0 to 12 months. Genomic DNA was extracted from dry blood spot samples, and polymerase chain reaction (PCR) was used to amplify exon 1 and exon 11 of the MEF2C gene. Due to resource constraints, 10 samples from cases and 10 from controls with adequate DNA quality were selected for sequencing. Sequence analysis was performed using BLAST and MEGA11 software, and the pathogenicity of identified variants was assessed using MutationTaster and Swiss-modeling tools.
Results: Among the sequenced samples, two non-synonymous MEF2C mutations were identified exclusively in CHD cases. A missense mutation (c.185T>A; p.M62K) was detected in an 8-month-old male with patent ductus arteriosus, while an insertion mutation (c.64_65insA; p.T22N) causing a frameshift and truncated protein was identified in an 8-month-old female with tetralogy of Fallot. These mutations were absent in all control samples and were predicted to be disease-causing.
Conclusion: This study identified potentially pathogenic MEF2C gene mutations among infants with CHD, suggesting a role of this gene in the disease pathogenesis. The findings highlight the importance of genetic studies in understanding CHD in low-resource settings and underscore the need for larger-scale genomic and functional studies to validate these associations.