Introduction: Even though the genetic nature of DCM is still poorly understood, numerous genes have been linked to it. These include genes that encode cytoskeleton, sarcomere, nuclear envelope, ion channels, and intercellular junction proteins. A diverse group of genes have been identified as dominant loci for the disease, which appears to have a genetic basis in over 20% of cases. Several of these gene's code for cytoskeletal proteins, suggesting that deficient force transmission is one of the leading causes of DCM. Nebulin-related anchoring protein (NRAP), which is expressed in the heart and striated muscles, is the second-largest actin-binding cytoskeletal protein in the nebulin family. NRAP, which is involved in the sarcomere contraction cycle, is one of the most recent genetic discoveries relating to DCM. Cases
Description: CASE 1: A 4-year-old boy a known case of dilated cardiomyopathy (DCM) and sickle cell trait presented to the emergency department with generalized body swelling, cough, and decreased urine output. His parents are closely related by positive consanguinity. His father died of a cardiac problem. On examination, afebrile, pulse 130 bpm, blood pressure 83/41 mmHg, he has cold extremities, capillary refills > 2 seconds. Abdominal examination revealed abdominal distention and tender hepatomegaly. Chest examination showed bilateral crepitation with bronchovesicular breathing. He has a pansystolic murmur with displaced apex beat on the background of normal S1 and S2. Electrocardiography showed normal sinus rhythm, right axis deviation, and left ventricular hypertrophy, with inverted T waves in the lateral lead. Echocardiography showed severe left ventricular depressed cardiac function with an 18% ejection fraction. he was admitted to the PICU and started on heart failure treatment. The full genetic workup-initiated report revealed NRAP gene mutation and patient transfer to high-level cardiac transplant center.
Discussion: In conclusion, the report presents three different cases of patients diagnosed with cardiomyopathy. We found that whole exome sequence showed A homozygous Autosomal recessive likely pathogenic variant was identified in the NRAP gene (NM_001261463.1:c.3568G>T p.(Glu1190*) which creates a premature stop codon. The condition was caused by the development of cardiomyocyte within the fetal heart. The cases also show that the homozygous gene in N-RAP can be inherited genetically by the patients from the first degree- and second-degree parents to cause cardiomyopathy. Also, a higher number of families are asymptomatic for a long time before establishment of the manifestations that comprise various symptoms like dilated cardiomyopathy, arrhythmias, and sudden death.
