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

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...

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Autores: Sanchez-Martinez, R, Iriarte, A, Mora-Lujan, JM, Patier, JL, Lopez-Wolf, D, Ojeda, A, Torralba, MA, Juyol, MC, Gil, R, Anon, S, Salazar-Mendiguchia, J, Riera-Mestre, A, Spanish Soc Internal Med
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p10881
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/10881
Access Level:acceso abierto
Palabra clave:Hereditary hemorrhagic telangiectasia
Genetic test
Phenotype
Genotype
Rare diseases
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network_acronym_str ES
network_name_str España
repository_id_str
spelling Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registrySanchez-Martinez, RIriarte, AMora-Lujan, JMPatier, JLLopez-Wolf, DOjeda, ATorralba, MAJuyol, MCGil, RAnon, SSalazar-Mendiguchia, JRiera-Mestre, ASpanish Soc Internal MedHereditary hemorrhagic telangiectasiaGenetic testPhenotypeGenotypeRare diseasesBackgroundHereditary 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.BMC2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/10881Orphanet Journal of Rare DiseasesISSN: 17501172reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p108812026-06-11T12:45:17Z
dc.title.none.fl_str_mv Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry
title Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry
spellingShingle Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry
Sanchez-Martinez, R
Hereditary hemorrhagic telangiectasia
Genetic test
Phenotype
Genotype
Rare diseases
title_short Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry
title_full Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry
title_fullStr Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry
title_full_unstemmed Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry
title_sort Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry
dc.creator.none.fl_str_mv Sanchez-Martinez, R
Iriarte, A
Mora-Lujan, JM
Patier, JL
Lopez-Wolf, D
Ojeda, A
Torralba, MA
Juyol, MC
Gil, R
Anon, S
Salazar-Mendiguchia, J
Riera-Mestre, A
Spanish Soc Internal Med
author Sanchez-Martinez, R
author_facet Sanchez-Martinez, R
Iriarte, A
Mora-Lujan, JM
Patier, JL
Lopez-Wolf, D
Ojeda, A
Torralba, MA
Juyol, MC
Gil, R
Anon, S
Salazar-Mendiguchia, J
Riera-Mestre, A
Spanish Soc Internal Med
author_role author
author2 Iriarte, A
Mora-Lujan, JM
Patier, JL
Lopez-Wolf, D
Ojeda, A
Torralba, MA
Juyol, MC
Gil, R
Anon, S
Salazar-Mendiguchia, J
Riera-Mestre, A
Spanish Soc Internal Med
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hereditary hemorrhagic telangiectasia
Genetic test
Phenotype
Genotype
Rare diseases
topic Hereditary hemorrhagic telangiectasia
Genetic test
Phenotype
Genotype
Rare diseases
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/10881
url https://fisabio.portalinvestigacion.com/publicaciones/10881
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv Orphanet Journal of Rare Diseases
ISSN: 17501172
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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