Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy
BACKGROUND The genetic cause of hypertrophic cardiomyopathy remains unexplained in a substantial proportion of cases. Formin homology 2 domain containing 3 (FHOD3) may have a role in the pathogenesis of cardiac hypertrophy but has not been implicated in hypertrophic cardiomyopathy. OBJECTIVES This s...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| Repositorio: | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| OAI Identifier: | oai:isabial.fundanetsuite.com:p2878 |
| Acceso en línea: | https://isabial.portalinvestigacion.com/publicaciones2878 |
| Access Level: | acceso abierto |
| Palabra clave: | cardiomyopathies FHOD3 formins genetics hypertrophic cardiomyopathy sudden death |
| id |
ES_012daa50fa8b0b0b4dae46e408dcb95d |
|---|---|
| oai_identifier_str |
oai:isabial.fundanetsuite.com:p2878 |
| network_acronym_str |
ES |
| network_name_str |
España |
| repository_id_str |
|
| dc.title.none.fl_str_mv |
Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy |
| title |
Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy |
| spellingShingle |
Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy Pablo Ochoa, Juan cardiomyopathies FHOD3 formins genetics hypertrophic cardiomyopathy sudden death |
| title_short |
Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy |
| title_full |
Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy |
| title_fullStr |
Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy |
| title_full_unstemmed |
Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy |
| title_sort |
Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic Cardiomyopathy |
| dc.creator.none.fl_str_mv |
Pablo Ochoa, Juan Sabater-Molina M Manuel Garcia-Pinilla, Jose Mogensen J Restrepo-Córdoba A Palomino-Doza J Villacorta E Martinez-Moreno M Ramos-Maqueda J Zorio E Pena-Pena, Maria L. García-Granja PE Rodríguez-Palomares JF Cardenas-Reyes, Ivonne J. de la Torre-Carpente, Maria M. Bautista-Paves, Alicia Akhtar, Mohammed M. Cicerchia, Marcos N. Bilbao-Quesada, Raquel Victoria Mogollon-Jimenez, Maria Salazar-Mendiguchia, Joel Mesa Latorre, Jose M. Arnaez, Blanca Olavarri-Miguel, Ivan Fuentes-Canamero, Maria E. Lamounier, Jr., Arsonval Perez Ruiz, Jose Maria Climent-Paya, Vicente Perez-Sanchez, Inmaculada Trujillo-Quintero, Juan P. Lopes, Luis R. Reparaz-Andrade, Alfredo Marin-Iglesias, Rosario Rodriguez-Vilela, Alejandro Sandin-Fuentes, Maria Garrote, Jose A. Cortel-Fuster, Alejandro Lopez-Garrido, Miguel Fontalba-Romero, Ana Ripoll-Vera, Tomas Llano-Rivas, Isabel Fernandez-Fernandez, Xusto Isidoro-Garcia, Maria Garcia-Giustiniani, Diego Barriales-Villa, Roberto Ortiz-Genga, Martin Garcia-Pavia, Pablo Elliott, Perry M. Gimeno, Juan R. Monserrat, Lorenzo |
| author |
Pablo Ochoa, Juan |
| author_facet |
Pablo Ochoa, Juan Sabater-Molina M Manuel Garcia-Pinilla, Jose Mogensen J Restrepo-Córdoba A Palomino-Doza J Villacorta E Martinez-Moreno M Ramos-Maqueda J Zorio E Pena-Pena, Maria L. García-Granja PE Rodríguez-Palomares JF Cardenas-Reyes, Ivonne J. de la Torre-Carpente, Maria M. Bautista-Paves, Alicia Akhtar, Mohammed M. Cicerchia, Marcos N. Bilbao-Quesada, Raquel Victoria Mogollon-Jimenez, Maria Salazar-Mendiguchia, Joel Mesa Latorre, Jose M. Arnaez, Blanca Olavarri-Miguel, Ivan Fuentes-Canamero, Maria E. Lamounier, Jr., Arsonval Perez Ruiz, Jose Maria Climent-Paya, Vicente Perez-Sanchez, Inmaculada Trujillo-Quintero, Juan P. Lopes, Luis R. Reparaz-Andrade, Alfredo Marin-Iglesias, Rosario Rodriguez-Vilela, Alejandro Sandin-Fuentes, Maria Garrote, Jose A. Cortel-Fuster, Alejandro Lopez-Garrido, Miguel Fontalba-Romero, Ana Ripoll-Vera, Tomas Llano-Rivas, Isabel Fernandez-Fernandez, Xusto Isidoro-Garcia, Maria Garcia-Giustiniani, Diego Barriales-Villa, Roberto Ortiz-Genga, Martin Garcia-Pavia, Pablo Elliott, Perry M. Gimeno, Juan R. Monserrat, Lorenzo |
| author_role |
author |
| author2 |
Sabater-Molina M Manuel Garcia-Pinilla, Jose Mogensen J Restrepo-Córdoba A Palomino-Doza J Villacorta E Martinez-Moreno M Ramos-Maqueda J Zorio E Pena-Pena, Maria L. García-Granja PE Rodríguez-Palomares JF Cardenas-Reyes, Ivonne J. de la Torre-Carpente, Maria M. Bautista-Paves, Alicia Akhtar, Mohammed M. Cicerchia, Marcos N. Bilbao-Quesada, Raquel Victoria Mogollon-Jimenez, Maria Salazar-Mendiguchia, Joel Mesa Latorre, Jose M. Arnaez, Blanca Olavarri-Miguel, Ivan Fuentes-Canamero, Maria E. Lamounier, Jr., Arsonval Perez Ruiz, Jose Maria Climent-Paya, Vicente Perez-Sanchez, Inmaculada Trujillo-Quintero, Juan P. Lopes, Luis R. Reparaz-Andrade, Alfredo Marin-Iglesias, Rosario Rodriguez-Vilela, Alejandro Sandin-Fuentes, Maria Garrote, Jose A. Cortel-Fuster, Alejandro Lopez-Garrido, Miguel Fontalba-Romero, Ana Ripoll-Vera, Tomas Llano-Rivas, Isabel Fernandez-Fernandez, Xusto Isidoro-Garcia, Maria Garcia-Giustiniani, Diego Barriales-Villa, Roberto Ortiz-Genga, Martin Garcia-Pavia, Pablo Elliott, Perry M. Gimeno, Juan R. Monserrat, Lorenzo |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
cardiomyopathies FHOD3 formins genetics hypertrophic cardiomyopathy sudden death |
| topic |
cardiomyopathies FHOD3 formins genetics hypertrophic cardiomyopathy sudden death |
| description |
BACKGROUND The genetic cause of hypertrophic cardiomyopathy remains unexplained in a substantial proportion of cases. Formin homology 2 domain containing 3 (FHOD3) may have a role in the pathogenesis of cardiac hypertrophy but has not been implicated in hypertrophic cardiomyopathy. OBJECTIVES This study sought to investigate the relation between FHOD3 mutations and the development of hypertrophic cardiomyopathy. METHODS FHOD3 was sequenced by massive parallel sequencing in 3,189 hypertrophic cardiomyopathy unrelated probands and 2,777 patients with no evidence of cardiomyopathy (disease control subjects). The authors evaluated protein-altering candidate variants in FHOD3 for cosegregation, clinical characteristics, and outcomes. RESULTS The authors identified 94 candidate variants in 132 probands. The variants' frequencies were significantly higher in patients with hypertrophic cardiomyopathy (74 of 3,189 [2.32%]) than in disease control subjects (18 of 2,777 [0.65%]; p < 0.001) or in the gnomAD database (1,049 of 138,606 [0.76%]; p < 0.001). FHOD3 mutations cosegregated with hypertrophic cardiomyopathy in 17 families, with a combined logarithm of the odds score of 7.92, indicative of very strong segregation. One-half of the disease-causing variants were clustered in a small conserved coiled-coil domain (amino acids 622 to 655); odds ratio for hypertrophic cardiomyopathy was 21.8 versus disease control subjects (95% confidence interval: 1.3 to 37.9; p < 0.001) and 14.1 against gnomAD (95% confidence interval: 6.9 to 28.7; p < 0.001). Hypertrophic cardiomyopathy patients carrying (likely) pathogenic mutations in FHOD3 (n = 70) were diagnosed after age 30 years (mean 46.1 +/- 18.7 years), and two-thirds (66%) were males. Of the patients, 82% had asymmetric septal hypertrophy (mean 18.8 +/- 5 mm); left ventricular ejection fraction <50% was present in 14% and hypertrabeculation in 16%. Events were rare before age 30 years, with an annual cardiovascular death incidence of 1% during follow-up. CONCLUSIONS FHOD3 is a novel disease gene in hypertrophic cardiomyopathy, accounting for approximately 1% to 2% of cases. The phenotype and the rate of cardiovascular events are similar to those reported in unselected cohorts. The FHOD3 gene should be routinely included in hypertrophic cardiomyopathy genetic testing panels. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 |
| 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://isabial.portalinvestigacion.com/publicaciones2878 |
| url |
https://isabial.portalinvestigacion.com/publicaciones2878 |
| 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 |
ELSEVIER SCIENCE INC |
| publisher.none.fl_str_mv |
ELSEVIER SCIENCE INC |
| dc.source.none.fl_str_mv |
JACC-JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY ISSN: 07351097 ISSNe: 15583597 reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante instname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| instname_str |
Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| reponame_str |
r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| collection |
r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869402563336470528 |
| spelling |
Formin Homology 2 Domain Containing 3 (FHOD3) Is a Genetic Basis for Hypertrophic CardiomyopathyPablo Ochoa, JuanSabater-Molina MManuel Garcia-Pinilla, JoseMogensen JRestrepo-Córdoba APalomino-Doza JVillacorta EMartinez-Moreno MRamos-Maqueda JZorio EPena-Pena, Maria L.García-Granja PERodríguez-Palomares JFCardenas-Reyes, Ivonne J.de la Torre-Carpente, Maria M.Bautista-Paves, AliciaAkhtar, Mohammed M.Cicerchia, Marcos N.Bilbao-Quesada, RaquelVictoria Mogollon-Jimenez, MariaSalazar-Mendiguchia, JoelMesa Latorre, Jose M.Arnaez, BlancaOlavarri-Miguel, IvanFuentes-Canamero, Maria E.Lamounier, Jr., ArsonvalPerez Ruiz, Jose MariaCliment-Paya, VicentePerez-Sanchez, InmaculadaTrujillo-Quintero, Juan P.Lopes, Luis R.Reparaz-Andrade, AlfredoMarin-Iglesias, RosarioRodriguez-Vilela, AlejandroSandin-Fuentes, MariaGarrote, Jose A.Cortel-Fuster, AlejandroLopez-Garrido, MiguelFontalba-Romero, AnaRipoll-Vera, TomasLlano-Rivas, IsabelFernandez-Fernandez, XustoIsidoro-Garcia, MariaGarcia-Giustiniani, DiegoBarriales-Villa, RobertoOrtiz-Genga, MartinGarcia-Pavia, PabloElliott, Perry M.Gimeno, Juan R.Monserrat, LorenzocardiomyopathiesFHOD3forminsgeneticshypertrophic cardiomyopathysudden deathBACKGROUND The genetic cause of hypertrophic cardiomyopathy remains unexplained in a substantial proportion of cases. Formin homology 2 domain containing 3 (FHOD3) may have a role in the pathogenesis of cardiac hypertrophy but has not been implicated in hypertrophic cardiomyopathy. OBJECTIVES This study sought to investigate the relation between FHOD3 mutations and the development of hypertrophic cardiomyopathy. METHODS FHOD3 was sequenced by massive parallel sequencing in 3,189 hypertrophic cardiomyopathy unrelated probands and 2,777 patients with no evidence of cardiomyopathy (disease control subjects). The authors evaluated protein-altering candidate variants in FHOD3 for cosegregation, clinical characteristics, and outcomes. RESULTS The authors identified 94 candidate variants in 132 probands. The variants' frequencies were significantly higher in patients with hypertrophic cardiomyopathy (74 of 3,189 [2.32%]) than in disease control subjects (18 of 2,777 [0.65%]; p < 0.001) or in the gnomAD database (1,049 of 138,606 [0.76%]; p < 0.001). FHOD3 mutations cosegregated with hypertrophic cardiomyopathy in 17 families, with a combined logarithm of the odds score of 7.92, indicative of very strong segregation. One-half of the disease-causing variants were clustered in a small conserved coiled-coil domain (amino acids 622 to 655); odds ratio for hypertrophic cardiomyopathy was 21.8 versus disease control subjects (95% confidence interval: 1.3 to 37.9; p < 0.001) and 14.1 against gnomAD (95% confidence interval: 6.9 to 28.7; p < 0.001). Hypertrophic cardiomyopathy patients carrying (likely) pathogenic mutations in FHOD3 (n = 70) were diagnosed after age 30 years (mean 46.1 +/- 18.7 years), and two-thirds (66%) were males. Of the patients, 82% had asymmetric septal hypertrophy (mean 18.8 +/- 5 mm); left ventricular ejection fraction <50% was present in 14% and hypertrabeculation in 16%. Events were rare before age 30 years, with an annual cardiovascular death incidence of 1% during follow-up. CONCLUSIONS FHOD3 is a novel disease gene in hypertrophic cardiomyopathy, accounting for approximately 1% to 2% of cases. The phenotype and the rate of cardiovascular events are similar to those reported in unselected cohorts. The FHOD3 gene should be routinely included in hypertrophic cardiomyopathy genetic testing panels. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).ELSEVIER SCIENCE INC2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://isabial.portalinvestigacion.com/publicaciones2878JACC-JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGYISSN: 07351097ISSNe: 15583597reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p28782026-06-12T10:20:37Z |
| score |
15,81155 |