Clinical and genetic profiles of hereditary transthyretin amyloidosis in Taiwan

• Published in: Annals of clinical and translational neurology 2019-05, Vol.6 (5), p.913-922
• Main Authors: Chao, Hua‐Chuan, Liao, Yi‐Chu, Liu, Yo‐Tsen, Guo, Yuh‐Cherng, Chang, Fu‐Pang, Lee, Yi‐Chung, Lin, Kon‐Ping
• Format: Article
• Language: English
• Subjects: Aged; Amyloid Neuropathies, Familial - genetics; Amyloidosis; Asians; Biopsy; Cardiomyopathy; Cohort Studies; Female; Genetic Profile; Genotype; Genotype & phenotype; Haplotypes; Humans; Male; Medical imaging; Middle Aged; Mutation; Peripheral neuropathy; Phenotype; Polymorphism, Single Nucleotide; Rectum - pathology; Taiwan - epidemiology
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.778

Objective The clinical and genetic profiles of hereditary transthyretin amyloidosis (ATTR) in Chinese populations remain elusive. We aim to characterize the features of ATTR in a Taiwanese cohort of Han Chinese descent. Methods Seventy‐nine patients with molecularly confirmed ATTR from 57 Taiwanese families were identified by sequencing the transthyretin gene (TTR). The clinical and electrophysiological data were scrutinized. Cardiac involvement of ATTR was evaluated by echocardiography and cardiac scintigraphy. Four microsatellite and seven single‐nucleotide polymorphism markers flanking TTR were genotyped to investigate the founder effect of the TTR Ala97Ser mutation. Results Most of the patients had a peripheral neuropathy with variable autonomic symptoms. The average age at disease onset (AO) was 58.2 ± 7.2 years, and the male patients had an earlier AO than female patients (56.6 ± 5.7 years vs. 61.8 ± 8.9 years, P = 0.013). Electrophysiological studies revealed a generalized axonal sensorimotor polyneuropathy and isolated median neuropathy in 84.5% and 15.5% of the patients, respectively. Up to 80% of the patients with ATTR had symptomatic or subclinical cardiac involvement. Six TTR mutations were identified in the participants including one novel mutation Glu89Asp. Among them, Ala97Ser was the most common mutation, accounting for 91.2% of the ATTR pedigrees. Detailed haplotype analyses demonstrated a shared haplotype in the 47 patients with the Ala97Ser mutation, suggesting a founder effect. Interpretation The present study delineates the distinct features of ATTR in Taiwan and provides useful information for the diagnosis and management of ATTR, especially in patients of Chinese descent.