Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis

This NEJM brief report describes two Filipino siblings with cardiomyopathy, hypertension, arrhythmia, and isolated left atrial fibrosis caused by a homozygous null frameshift variant in the CORIN gene (c.684dupG; p.Met229Aspfs*16). Corin is the atrial natriuretic peptide (ANP)-converting enzyme. Both siblings showed absent plasma corin and NT-proANP levels, moderately elevated BNP, and increased fibrosis markers (notably PICP). Functional assays showed impaired ENaC regulation and suboptimal cGMP production, reflecting a defective ANP pathway. Despite elevated BNP, it did not compensate for corin deficiency. Imaging revealed left atrial enlargement and low-voltage electroanatomical mapping consistent with atrial fibrosis. Family history revealed early-onset hypertension among heterozygous carriers. The editorial supports corin’s critical role in ANP activation, left atrial structure and function, and cardiovascular homeostasis. It calls attention to the translational potential of corin-targeted therapies and raises genetic susceptibility considerations in Southeast Asian populations.

This NEJM brief report describes two Filipino siblings with cardiomyopathy, hypertension, arrhythmia, and isolated left atrial fibrosis caused by a homozygous null frameshift variant in the CORIN gene (c.684dupG; p.Met229Aspfs*16). Corin is the atrial natriuretic peptide (ANP)-converting enzyme. Both siblings showed absent plasma corin and NT-proANP levels, moderately elevated BNP, and increased fibrosis markers (notably PICP). Functional assays showed impaired ENaC regulation and suboptimal cGMP production, reflecting a defective ANP pathway. Despite elevated BNP, it did not compensate for corin deficiency. Imaging revealed left atrial enlargement and low-voltage electroanatomical mapping consistent with atrial fibrosis. Family history revealed early-onset hypertension among heterozygous carriers. The editorial supports corin’s critical role in ANP activation, left atrial structure and function, and cardiovascular homeostasis. It calls attention to the translational potential of corin-targeted therapies and raises genetic susceptibility considerations in Southeast Asian populations.