dc.contributor.author | De Frutos, Fernando | |
dc.contributor.author | Ochoa, Juan Pablo | |
dc.contributor.author | García Pavía, Pablo | |
dc.date.accessioned | 2023-06-12T10:50:52Z | |
dc.date.available | 2023-06-12T10:50:52Z | |
dc.date.issued | 2022 | |
dc.identifier.issn | 1350-6129 | spa |
dc.identifier.uri | https://hdl.handle.net/10641/3400 | |
dc.description.abstract | Background
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.
Methods
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.
Results
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 (p < 0.001). Haplotype analysis revealed a common origin from an ancestor who lived ∼500 years ago in southeast Spain.
Conclusions
Glu89Lys ATTRv is a TTR 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. | spa |
dc.language.iso | eng | spa |
dc.publisher | Amyloid | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | Amyloidosis | spa |
dc.subject | Founder effect | spa |
dc.subject | Hereditary ATTR | spa |
dc.subject | Glu89Lys | spa |
dc.subject | Transthyretin | spa |
dc.title | Phenotype and clinical outcomes of Glu89Lys hereditary transthyretin amyloidosis: a new endemic variant in Spain. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dc.rights.accessRights | open access | spa |
dc.description.extent | 2555 KB | spa |
dc.identifier.doi | 10.1080/13506129.2022.2142110 | spa |
dc.relation.publisherversion | https://www.tandfonline.com/doi/full/10.1080/13506129.2022.2142110 | spa |