Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry

Data de publicació: 05/06/2020 Data Ahead of Print: 05/06/2020

Autors de IIS La Fe

Ricardo Gil Sánchez

Autor

Autors aliens a IIS La Fe

Sanchez-Martinez, R
Iriarte, A
Mora-Lujan, JM
Patier, JL
Lopez-Wolf, D
Ojeda, A
Torralba, MA
Juyol, MC
Anon, S
Salazar-Mendiguchia, J
Riera-Mestre, A

Grups d'Investigació

Investigacion clínica en enfermedades crónicas e Infección por el VIH

Investigador establecido

Marta Montero Alonso

Abstract

BackgroundHereditary hemorrhagic telangiectasia (HHT) is a rare vascular disease with autosomal dominant inheritance. Disease-causing variants in endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes are detected in more than 90% of cases submitted to molecular diagnosis.MethodsWe used data from the RiHHTa (Computerized Registry of Hereditary Hemorrhagic Telangiectasia) registry to describe genetic variants and to assess their genotype-phenotype correlation among HHT patients in Spain.ResultsBy May 2019, 215 patients were included in the RiHHTa registry with a mean age of 52.516.5years and 136 (63.3%) were women. Definitive HHT diagnosis defined by the Curacao criteria were met by 172 (80%) patients. Among 113 patients with genetic test, 77 (68.1%) showed a genetic variant in ACVRL1 and 36 (31.8%) in ENG gene. The identified genetic variants in ACVRL1 and ENG genes and their clinical significance are provided. ACVRL1 mutations were more frequently nonsense (50%) while ENG mutations were more frequently, frameshift (39.1%). ENG patients were significantly younger at diagnosis (36.9 vs 45.7years) and had pulmonary arteriovenous malformations (AVMs) (71.4% vs 24.4%) and cerebral AVMs (17.6% vs 2%) more often than patients with ACVRL1 variants. Patients with ACVRL1 variants had a higher cardiac index (2.62 vs 3.46), higher levels of hepatic functional blood tests, and anemia (28.5% vs 56.7%) more often than ENG patients.Conclusions ACVRL1 variants are more frequent than ENG in Spain. ACVRL1 patients developed symptomatic liver disease and anemia more often than ENG patients. Compared to ACVRL1, those with ENG variants are younger at diagnosis and show pulmonary and cerebral AVMs more frequently.

Dades de la publicació

ISSN/ISSNe:: 1750-1172, 1750-1172
Tipus:: Article
Pàgines:: 138-138
DOI:: 10.1186/s13023-020-01422-8
PubMed:: 32503579
Factor d'Impacte:: 1,274 SCImago ℠
Quartil:: Q1 SCImago ℠

Documents

No hi ha documents

Mètriques

Filiacions

Sanchez-Martinez, R:: Hosp Gen Univ Alicante, Internal Med Dept, ISABIAL, Alicante, Spain

Spanish Soc Internal Med, Rare Dis Working Grp, Madrid, Spain
Iriarte, A:: Spanish Soc Internal Med, Rare Dis Working Grp, Madrid, Spain

Hosp Univ Bellvitge, Internal Med Dept, Hereditary Hemorrhag Telangiectasia Unit, IDIBELL, Feixa Llarga S-N, Barcelona 08907, Spain
Mora-Lujan, JM:: Spanish Soc Internal Med, Rare Dis Working Grp, Madrid, Spain

Hosp Univ Bellvitge, Internal Med Dept, Hereditary Hemorrhag Telangiectasia Unit, IDIBELL, Feixa Llarga S-N, Barcelona 08907, Spain
Patier, JL:: Spanish Soc Internal Med, Rare Dis Working Grp, Madrid, Spain

Univ Alcala De Henares, Univ Hosp Ramon & Cajal, Dept Internal Med, Syst & Orphan Dis Unit,IRYCIS, Madrid, Spain
Lopez-Wolf, D:: Spanish Soc Internal Med, Rare Dis Working Grp, Madrid, Spain

Hosp Univ Fdn Alcorcon, Internal Med Dept, Madrid, Spain
Ojeda, A:: Spanish Soc Internal Med, Rare Dis Working Grp, Madrid, Spain

Hosp Insular Univ Gran Canaria, Internal Med Dept, Gran Canaria, Spain
Torralba, MA:: Spanish Soc Internal Med, Rare Dis Working Grp, Madrid, Spain

Hosp Clin Univ Lozano Blesa, Internal Med Dept, Zaragoza, Spain
Juyol, MC:: Spanish Soc Internal Med, Rare Dis Working Grp, Madrid, Spain

Hosp Univ Miguel Servet, Internal Med Dept, Zaragoza, Spain
Gil, R:: Spanish Soc Internal Med, Rare Dis Working Grp, Madrid, Spain

Hosp La Fe, Internal Med Dept, Valencia, Spain
Anon, S:: Spanish Soc Internal Med, Rare Dis Working Grp, Madrid, Spain

Hosp Arnau Vilanova, Internal Med Dept, Valencia, Spain
Salazar-Mendiguchia, J:: Hlth Code, La Coruna, Spain

Hosp Univ Bellvitge, Clin Genet Program, IDIBELL, Barcelona, Spain

Univ Autonoma Barcelona, Genet Dept, Barcelona, Spain
Riera-Mestre, A:: Spanish Soc Internal Med, Rare Dis Working Grp, Madrid, Spain

Hosp Univ Bellvitge, Internal Med Dept, Hereditary Hemorrhag Telangiectasia Unit, IDIBELL, Feixa Llarga S-N, Barcelona 08907, Spain

Univ Barcelona, Fac Med & Hlth Sci, Barcelona, Spain

Keywords

Hereditary hemorrhagic telangiectasia; Genetic test; Phenotype; Genotype; Rare diseases

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