Abstract
Background: Dilated cardiomyopathy leads to contractile dysfunction, progressive heart failure, and excessive risk of sudden cardiac death. We reported a homozygous damaging variation in CAP2 causing dilated cardiomyopathy and supraventricular tachycardia in two cousins of one family. Additional homozygous mutations in CAP2 with clinical presentations were reported.
Aim: To present the different CAP2 mutations described in patients of various populations with a spectrum of clinical descriptions and possibly correlate the mutations to the clinical findings. This is important for the diagnosing and prognosis of patients with mutations in this gene.
Methods: Clinical evaluation of an additional patient of the family we previously reported. Literature searches of clinical studies of patients affected by mutations in CAP2, animal models for the gene, and the role of CAP2 in the assembly of actin in the thin filaments of the sarcomere.
Results: All patients had dilated cardiomyopathy necessitating heart transplants at a very young age. Two patients with one loss of function mutation presented additionally with structural heart abnormalities. Another loss of function mutation in one patient associated with nemaline myopathy, mild hypotonia, atrophic, and widened scarring. One report did not detail the patient's mutation and presented tricuspid and pulmonary atresia. Animal models of mice and sheep had additional defects not reported in human patients. The pathology is caused by the loss of the function of CAP2 in actin polymerization and in the “α-actin switch” occurring during differentiation and required for the sarcomere structure and function.
Conclusions: The homozygous mutations in CAP2 cause severe Dilated cardiomyopathy. Additional phenotypes may not be seen in all individuals, and the severity of the mutation and disease do not correlate.