Hereditary transthyretin amyloid cardiomyopathy caused by the rare TTR p.Ser43Asn variant in an Asian family: a case report

Background Transthyretin amyloid cardiomyopathy (ATTR–CM) is an infiltrative cardiomyopathy that may occur in hereditary or wild-type forms. Although more than 150 transthyretin ( TTR ) variants have been reported, the c.128G > A (p.Ser43Asn) variant is rare, and data from Asian populations remain limited. Case presentation This report describes a mainland Chinese family carrying the rare TTR c.128G > A (p.Ser43Asn) variant. The proband, a 51-year-old Chinese man, presented with exertional chest tightness and dyspnea. Electrocardiography showed left ventricular hypertrophy, while echocardiography demonstrated concentric left ventricular wall thickening, reduced systolic function, and relative apical sparing on strain imaging. Technetium-99 m pyrophosphate [(99 m)Tc-PYP] scintigraphy showed grade 3 myocardial uptake, and monoclonal protein assessment, including serum and urine immunofixation electrophoresis and serum free light-chain testing, did not support light-chain amyloidosis. Genetic testing identified a heterozygous c.128G > A (p.Ser43Asn) missense variant in the TTR gene. Tafamidis was initiated after diagnosis. On follow-up, the proband remained in New York Heart Association functional class II, with persistent structural cardiac abnormalities on echocardiography. Family investigation identified additional affected relatives and carriers of the same variant, supporting a hereditary pattern of disease in this pedigree. Conclusion This family report expands the clinical spectrum associated with the rare TTR c.128G > A (p.Ser43Asn) variant and adds to the limited data available from Asian populations.