TY - JOUR
T1 - Phenotypic characteristics of F64L, I68L, I107V, and S77Y ATTRv genotypes from the Transthyretin Amyloidosis Outcomes Survey (THAOS)
AU - Gentile, Luca
AU - Diemberger, Igor
AU - Plante-Bordeneuve, Violaine
AU - Mazzeo, Anna
AU - Dori, Amir
AU - Luigetti, Marco
AU - Paolantonio, Andrea Di
AU - Dispenzieri, Angela
AU - Grogan, Martha
AU - Cruz, Márcia Waddington
AU - Adams, David
AU - Inamo, Jocelyn
AU - Kristen, Arnt V.
AU - Cirami, Calogero Lino
AU - Chapman, Doug
AU - Gupta, Pritam
AU - Glass, Oliver
AU - Amass, Leslie
N1 - Publisher Copyright:
Copyright: © 2024 Gentile et al.
PY - 2024/1
Y1 - 2024/1
N2 - Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multi-systemic disease with wild-type (ATTRwt) and hereditary (ATTRv) forms. Over 130 variants associated with ATTRv amyloidosis have been identified, although little is known about the majority of these genotypes. This analysis examined phenotypic characteristics of symptomatic patients with ATTRv amyloidosis enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS) with four less frequently reported pathogenic genotypes: F64L (c.250T>C, p.F84L), I68L (c.262A>T, p.I88L), I107V (c.379A>G; p.I127V), and S77Y (c.290C>A; p.S97Y). THAOS is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both ATTRwt and ATTRv amyloidosis. This analysis describes the baseline demographic and clinical characteristics of untreated symptomatic patients with the F64L, I68L, I107V, or S77Y genotypes at enrollment in THAOS (data cutoff date: January 4, 2022). There were 141 symptomatic patients with F64L (n = 46), I68L (n = 45), I107V (n = 21), or S77Y (n = 29) variants at the data cutoff. Most patients were male and median age at enrollment was in the sixth decade for S77Y patients and the seventh decade for the others. A predominantly neurologic phenotype was associated with F64L, I107V, and S77Y genotypes, whereas patients with the I68L genotype presented with more pronounced cardiac involvement. However, a mixed phenotype was also reported in a considerable proportion of patients in each variant subgroup. This analysis from THAOS represents the largest study of ATTRv symptomatic patients with the F64L, I68L, I107V, and S77Y genotypes. These data add to the limited knowledge on the clinical profile of patients with specific ATTRv variants and emphasize the importance of comprehensive assessment of all patients.
AB - Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multi-systemic disease with wild-type (ATTRwt) and hereditary (ATTRv) forms. Over 130 variants associated with ATTRv amyloidosis have been identified, although little is known about the majority of these genotypes. This analysis examined phenotypic characteristics of symptomatic patients with ATTRv amyloidosis enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS) with four less frequently reported pathogenic genotypes: F64L (c.250T>C, p.F84L), I68L (c.262A>T, p.I88L), I107V (c.379A>G; p.I127V), and S77Y (c.290C>A; p.S97Y). THAOS is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both ATTRwt and ATTRv amyloidosis. This analysis describes the baseline demographic and clinical characteristics of untreated symptomatic patients with the F64L, I68L, I107V, or S77Y genotypes at enrollment in THAOS (data cutoff date: January 4, 2022). There were 141 symptomatic patients with F64L (n = 46), I68L (n = 45), I107V (n = 21), or S77Y (n = 29) variants at the data cutoff. Most patients were male and median age at enrollment was in the sixth decade for S77Y patients and the seventh decade for the others. A predominantly neurologic phenotype was associated with F64L, I107V, and S77Y genotypes, whereas patients with the I68L genotype presented with more pronounced cardiac involvement. However, a mixed phenotype was also reported in a considerable proportion of patients in each variant subgroup. This analysis from THAOS represents the largest study of ATTRv symptomatic patients with the F64L, I68L, I107V, and S77Y genotypes. These data add to the limited knowledge on the clinical profile of patients with specific ATTRv variants and emphasize the importance of comprehensive assessment of all patients.
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U2 - 10.1371/journal.pone.0292435
DO - 10.1371/journal.pone.0292435
M3 - Article
C2 - 38241252
AN - SCOPUS:85182804004
SN - 1932-6203
VL - 19
JO - PloS one
JF - PloS one
IS - 1 January
M1 - e0292435
ER -