Current HHT genetic overview in Spain and its phenotypic correlation : data from RiHHTa registry
Sánchez-Martínez, Rosario (Sociedad Española de Medicina Interna)
Iriarte, Adriana (Institut d'Investigació Biomèdica de Bellvitge)
Mora-Luján, José María (Institut d'Investigació Biomèdica de Bellvitge)
Patier, José Luis (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
López-Wolf, Daniel (Hospital Universitario Fundación Alcorcón)
Ojeda García, Ana (Hospital Universitario Insular de Gran Canaria)
Torralba, Miguel Angel (Hospital Clínico Universitario "Lozano Blesa" de Zaragoza)
Juyol, María Coloma (Hospital Universitario Miguel Servet (Saragossa))
Gil, Ricardo (Hospital Universitari i Politècnic La Fe (València))
Añón, Sol (Hospital Arnau de Vilanova (València))
Salazar-Mendiguchía, Joel (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Riera Mestre, Antoni (Universitat de Barcelona. Facultat de Medicina i Ciències de la Salut)

Data:	2020
Resum:	Hereditary 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. We 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. By May 2019, 215 patients were included in the RiHHTa registry with a mean age of 52. 5 ± 16. 5 years and 136 (63. 3%) were women. Definitive HHT diagnosis defined by the Curaçao 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. 7 years) 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. 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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Hereditary hemorrhagic telangiectasia ; Genetic test ; Phenotype ; Genotype ; Rare diseases
Publicat a:	Orphanet journal of rare diseases, Vol. 15 (June 2020) , art. 138, ISSN 1750-1172

DOI: 10.1186/s13023-020-01422-8
PMID: 32503579

8 p, 724.4 KB

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