Paula Navas Tejedor1, Julián Palomino Doza2, Jair Antonio Tenorio Castaño3, Ana Belén Enguita Valls4, José Julián Rodríguez Reguero5, Amaya Martínez Meñaca6, Ignacio Hernández González7, Héctor Bueno Zamora8, Pablo Daniel Lapunzina Badía3, Pilar Escribano Subías9. 1. Servicio de Cardiología, Hospital Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain. 2. Unidad de Cardiopatías Familiares, Servicio de Cardiología, Hospital Universitario 12 de Octubre, Madrid, Spain; Servicio de Cardiología, Hospital Universitario 12 de Octubre, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain. 3. Instituto de Genética Médica y Molecular (INGEMM), Instituto de Investigación La Paz (IdiPAZ), Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain. 4. Servicio de Anatomía Patológica, Hospital Universitario 12 de Octubre, Madrid, Spain. 5. Servicio de Cardiología, Hospital Central de Asturias, Oviedo, Asturias, Spain. 6. Servicio de Neumología, Hospital Universitario Marqués de Valdecilla, Santander, Cantabria, Spain. 7. Servicio de Cardiología, Hospital Universitario 12 de Octubre, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain; Unidad Multidisciplinar de Hipertensión Pulmonar, Servicio de Cardiología, Hospital Universitario 12 de Octubre, Madrid, Spain. 8. Servicio de Cardiología, Hospital Universitario 12 de Octubre, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. 9. Servicio de Cardiología, Hospital Universitario 12 de Octubre, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain; Unidad Multidisciplinar de Hipertensión Pulmonar, Servicio de Cardiología, Hospital Universitario 12 de Octubre, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: mariapilar.escribano@salud.madrid.org.
Abstract
INTRODUCTION AND OBJECTIVES: Hereditary pulmonary veno-occlusive disease (PVOD) has been associated with biallelic mutations in EIF2AK4 with the recent discovery of a founder mutation in Iberian Romani patients with familial PVOD. The aims of this study were phenotypical characterization and survival analysis of Iberian Romani patients with familial PVOD carrying the founder p.Pro1115Leu mutation in EIF2AK4, according to their tolerance to pulmonary vasodilators (PVD). Familial genetic screening was conducted, as well as assessment of sociocultural determinants with a potential influence on disease course. METHODS: Observational study of Romani patients with familial PVOD included in the Spanish Registry of Pulmonary Arterial Hypertension. Genetic screening of EIF2AK4 was performed in index cases and relatives between November 2011 and July 2016 and histological pulmonary examination was carried out in patients who received a lung transplant or died. The patients were divided into 2 groups depending on their tolerance to PVD, with comparison of baseline characteristics and survival free of death or lung transplant. RESULTS: Eighteen Romani patients were included: 9 index cases and 9 relatives. The biallelic founder mutation in EIF2AK4 was found in all affected cases and 2 unaffected relatives. Family screening showed 34.2% of healthy heterozygotes, high consanguinity, young age at childbirth, and frequent multiparity. Prognosis was bleak, with significant differences depending on tolerance to PVD. CONCLUSIONS: We describe 2 phenotypes of hereditary PVOD depending on tolerance to PVD, with prognostic impact and familial distribution. Consanguinity may have a negative impact on the transmission of PVOD, with familial genetic screening showing high effectiveness.
INTRODUCTION AND OBJECTIVES:Hereditary pulmonary veno-occlusive disease (PVOD) has been associated with biallelic mutations in EIF2AK4 with the recent discovery of a founder mutation in Iberian Romani patients with familial PVOD. The aims of this study were phenotypical characterization and survival analysis of Iberian Romani patients with familial PVOD carrying the founder p.Pro1115Leu mutation in EIF2AK4, according to their tolerance to pulmonary vasodilators (PVD). Familial genetic screening was conducted, as well as assessment of sociocultural determinants with a potential influence on disease course. METHODS: Observational study of Romani patients with familial PVOD included in the Spanish Registry of Pulmonary Arterial Hypertension. Genetic screening of EIF2AK4 was performed in index cases and relatives between November 2011 and July 2016 and histological pulmonary examination was carried out in patients who received a lung transplant or died. The patients were divided into 2 groups depending on their tolerance to PVD, with comparison of baseline characteristics and survival free of death or lung transplant. RESULTS: Eighteen Romani patients were included: 9 index cases and 9 relatives. The biallelic founder mutation in EIF2AK4 was found in all affected cases and 2 unaffected relatives. Family screening showed 34.2% of healthy heterozygotes, high consanguinity, young age at childbirth, and frequent multiparity. Prognosis was bleak, with significant differences depending on tolerance to PVD. CONCLUSIONS: We describe 2 phenotypes of hereditary PVOD depending on tolerance to PVD, with prognostic impact and familial distribution. Consanguinity may have a negative impact on the transmission of PVOD, with familial genetic screening showing high effectiveness.
Authors: Teresa Segura de la Cal; Carmen Pérez-Olivares; María José Cristo Ropero; Raquel Luna López; Pilar Escribano-Subías Journal: Eur Heart J Case Rep Date: 2022-03-28
Authors: Ignacio Hernandez-Gonzalez; Jair Tenorio; Julian Palomino-Doza; Amaya Martinez Meñaca; Rafael Morales Ruiz; Mauro Lago-Docampo; María Valverde Gomez; Javier Gomez Roman; Ana Belén Enguita Valls; Carmen Perez-Olivares; Diana Valverde; Joan Gil Carbonell; Elvira Garrido-Lestache Rodríguez-Monte; Maria Jesus Del Cerro; Pablo Lapunzina; Pilar Escribano-Subias Journal: PLoS One Date: 2020-04-29 Impact factor: 3.240
Authors: Marta Pérez Núñez; Sergio Alonso Charterina; Carmen Pérez-Olivares; Yolanda Revilla Ostolaza; Rafael Morales Ruiz; Ana Belén Enguita Valls; Jair Antonio Tenorio; Natalia Gallego Zazo; Alicia De Pablo Gafas; Pablo Lapunzina; Adriana Rodríguez Chaverri; Pilar Escribano Subías Journal: Diagnostics (Basel) Date: 2021-01-19