A Single-Kindred Cluster of Val122Ile Transthyretin Amyloid Cardiomyopathy: Subclinical Case Series of Three Japanese Patients

Intern Med. 2026 Mar 17. doi: 10.2169/internalmedicine.6926-25. Online ahead of print.

Abstract

Transthyretin Val122Ile variant carriers are at risk of developing heart failure, with this variant being observed in individuals of Western African ancestry. We encountered three patients carrying this variant in a single kindred from southern Japan. The detection of amyloid in the carpal tunnel tissue prompted comprehensive clinical evaluation, confirming cardiac involvement. Speckle-tracking echocardiography and cardiac magnetic resonance imaging revealed age-related progression of myocardial involvement predominantly affecting the basal inferoseptum. The transthyretin Val122Ile variant is associated with poor clinical outcomes. Clinicians should be aware that this variant can also be sporadically present in elderly Japanese patients with cardiomyopathy or heart failure.

Keywords: Val1221Ile; amyloidosis; speckle-tracking echocardiography; transthyretin.