title: Asp58Ala is the predominant mutation of the TTR gene in Korean patients with hereditary transthyretin-related amyloidosis.
abstract: Hereditary transthyretin (TTR)-related amyloidosis (ATTR) seems to be a rare autosomal-dominant inherited form of systemic amyloidosis. Studies indicate considerable heterogeneity in the disease's presentation and genotype; however, there is little data from Korea, where the prevalence of hereditary ATTR is very low. In this study, we investigated the phenotypic and genotypic spectra of hereditary ATTR in Korea. Direct sequencing analysis was performed to detect TTR gene mutations in amyloidosis patients whose results of TTR immunohistochemical staining were positive or equivocal. Clinical presentation was categorized as exclusively cardiac, exclusively neurologic, or mixed phenotype. Of 12 genetic tests performed, seven were positive for TTR mutations. D58A (c.173A>C) was the most common mutation in this study (57%, 4/7). The majority of those patients with hereditary ATTR had the mixed phenotype (86%, 6/7). The patients with D58A mutation had older ages of disease onset (median, 61 years vs. 42 years; P = 0.08), and a higher incidence of gastrointestinal involvement (75% vs. 0%; P = 0.03) than those with other identified TTR mutations. A significant male predominance was also noted in this study (P = 0.01).
authors: Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Mi-Ae
authors: MA
authors: Jang
authors: Ga Yeon
authors: GY
authors: Lee
authors: Kihyun
authors: K
authors: Kim
authors: Seok-Jin
authors: SJ
authors: Kim
authors: Jung-Sun
authors: JS
authors: Kim
authors: Soo-Youn
authors: SY
authors: Lee
authors: Hee-Jin
authors: HJ
authors: Kim
authors: Eun-Seok
authors: ES
authors: Jeon
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D028227:Amyloid Neuropathies, Familial / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D056910:Republic of Korea
keywords: D58A; Korea; TTR; hereditary; transthyretin-related amyloidosis