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Phenotype and clinical outcomes of Glu89Lys hereditary transthyretin amyloidosis: a new endemic variant in Spain.

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • de Frutos, Fernando
  • Ochoa, Juan Pablo
  • Gomez-Gonzalez, Cristina
  • Reyes-Leiva, David
  • Aróstegui JI
  • Barriales-Villa, Roberto
  • Gonzalez-Lopez, Esther
  • Ramil, Elvira
  • Galan, Lucia
  • Gonzalez-Costello, Jose
  • Garcia-Alvarez, Ana
  • Rojas-Garcia, Ricard
  • Espinosa MA
  • Garcia-Pavia, Pablo

Grupos

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.

Datos de la publicación

ISSN/ISSNe:
1350-6129, 1744-2818

AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS  TAYLOR & FRANCIS LTD

Tipo:
Article
Páginas:
1-9
PubMed:
36343383
Enlace a otro recurso:
www.scopus.com
Factor de Impacto:
1,706 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 12

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Keywords

  • Amyloidosis; Glu89Lys; founder effect; hereditary ATTR; transthyretin

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