Hereditary Transthyretin Amyloidosis- Clinical and Genetic Characteristics of a Multiracial South-East Asian Cohort in Singapore

Studies of hereditary transthyretin amyloidosis (ATTRv amyloidosis) in South-East Asia are underrepresented in the literature. We report the unique phenotypic and genetic characteristics of this disorder in a multiracial South-East Asian cohort. Patients with genetically proven ATTRv amyloidosis wer...

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Bibliographic Details
Published in:	Journal of neuromuscular diseases Vol. 8; no. 4; p. 723
Main Authors:	Chen, Zhiyong, Koh, Jasmine S, Saini, Monica, Tay, Karine S S, Jayne Tan, Yi, Chai, Josiah Y H, Fam, Su Rong, Juraidah, A R, Lim, Peck Kee, Ng, Adeline S L, Prasad, Kalpana, Tan, Chai Beng, Umapathi, T, Verma, Kamal K, Yong, Ming Hui, Yu, Chen, Ng, Peng Soon
Format:	Journal Article
Language:	English
Published:	Netherlands 01-01-2021
Subjects:	Adult Aged Amyloid Neuropathies, Familial - genetics Asia, Southeastern Carpal Tunnel Syndrome - genetics Cohort Studies Female Genotype Humans Male Middle Aged Mutation Retrospective Studies Singapore Asia, Southeastern Singapore familial amyloidosis hereditary TTR protein Amyloid neuropathies human transthyretin-related
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Summary:	Studies of hereditary transthyretin amyloidosis (ATTRv amyloidosis) in South-East Asia are underrepresented in the literature. We report the unique phenotypic and genetic characteristics of this disorder in a multiracial South-East Asian cohort. Patients with genetically proven ATTRv amyloidosis were identified over a 13-year period (2007-2020) at the National Neuroscience Institute, Singapore. Clinical, laboratory, genotypic and electrophysiological features were retrospectively reviewed. 29 patients comprising Chinese, Malay, Burmese, Vietnamese and Indonesians with ATTRv amyloidosis were identified. Somatic neuropathy was the most common initial presentation, followed by carpal tunnel syndrome, autonomic dysfunction and cardiac dysfunction. ATTR-A97S (p.Ala117Ser) was the most common variant found in 14 patients, constituting 66.7%of ethnic Chinese patients and 48.3%of the entire cohort. Five patients had early-onset disease (age < 50 years) with the following variants: ATTR-V30M (p.Val50Met), ATTR-G47A (p.Gly67Ala), ATTR-S50I (p.Ser70Ile) and ATTR-A97S (p.Ala117Ser); one patient with ATTR-A97S (p.Ala117Ser) had isolated unilateral carpal tunnel syndrome with amyloid deposits identified on histological examination of the transverse carpal ligament. All early-onset patients had a positive parental history; two patients, with ATTR-S50I (p.Ser70Ile) and ATTR-Ala97Ser (p.Ala117Ser) respectively, demonstrated anticipation with mother-to-daughter inheritance. Amongst the 24 patients with late-onset disease (age≥50 years), two patients had novel variants, ATTR-G66D (p.Glu86Asp) and ATTR-A81V (p.Ala101Val) that were confirmed to be pathogenic based on the histological identification of transthyretin amyloid. Other identified variants included ATTR-V30M (p.Val50Met), ATTR-R34T (p.Arg54Thr), ATTR-S50I (p.Ser70Ile), ATTR-H88R (p.His108Arg) and ATTR-A97S (p.Ala117Ser). Our study further expands the genotypic and phenotypic knowledge regarding ATTRv amyloidosis.
ISSN:	2214-3602
DOI:	10.3233/JND-210656