10.6084/M9.FIGSHARE.21514230.V1
Fernando de Frutos
Fernando
de Frutos
Juan Pablo Ochoa
Juan Pablo
Ochoa
Cristina Gómez-González
Cristina
Gómez-González
David Reyes-Leiva
David
Reyes-Leiva
Juan I. Aróstegui
Juan I.
Aróstegui
Carlos Casasnovas
Carlos
Casasnovas
Bellvitge University Hospital
Institut d'Investigació Biomédica de Bellvitge
Centro de Investigación Biomédica en Red de Enfermedades Raras
Roberto Barriales-Villa
Roberto
Barriales-Villa
Teresa Sevilla
Teresa
Sevilla
Esther Gonzalez-Lopez
Esther
Gonzalez-Lopez
Elvira Ramil
Elvira
Ramil
Lucia Galan
Lucia
Galan
Jose González-Costello
Jose
González-Costello
Ana García-Álvarez
Ana
García-Álvarez
Ricard Rojas-Garcia
Ricard
Rojas-Garcia
Maria Angeles Espinosa
Maria Angeles
Espinosa
Pablo Garcia-Pavia
Pablo
Garcia-Pavia
Phenotype and clinical outcomes of Glu89Lys hereditary transthyretin amyloidosis: a new endemic variant in Spain
<p>The p.Glu109Lys variant (Glu89Lys) is a rare cause of hereditary transthyretin amyloidosis (ATTRv) for which clinical spectrum remains unresolved. We sought to describe the clinical characteristics and outcomes of ATTR Glu89Lys amyloidosis and assess a potential founder effect in Spain.</p> <p>Patients with the p.Glu109Lys ATTRv variant from 14 families were recruited at 7 centres. Demographics, complementary tests and clinical course were analysed. Haplotype analysis was performed in 7 unrelated individuals.</p> <p>Thirty-eight individuals (13 probands, mean age 40.4 ± 13.1 years) were studied. After median follow-up of 5.1 years (IQR 1.7–9.6), 7 patients died and 7 required heart transplantation (median age at transplantation 50.5 years). Onset of cardiac and neurological manifestations occurred at a mean age of 48.4 and 46.8 years, respectively. Median survival from birth was 61.6 years and no individual survived beyond 65 years. Patients treated with disease-modifying therapies exhibited better prognosis (<i>p</i> < 0.001). Haplotype analysis revealed a common origin from an ancestor who lived ∼500 years ago in southeast Spain.</p> <p>Glu89Lys ATTRv is a <i>TTR</i> variant with a founder effect in Spain. It is associated with near complete penetrance, early onset and mixed cardiac and neurologic phenotype. Patients have poor prognosis, particularly if not treated with disease-modifying therapies.</p>
Medicine
Biotechnology
Sociology
Biological Sciences not elsewhere classified
Science Policy
Virology
Taylor & Francis
2022
2022-11-07
2023-07-14
Journal contribution
238273 Bytes
10.6084/m9.figshare.21514230
10.1080/13506129.2022.2142110
CC BY 4.0