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Novel Genetic and Molecular Pathways in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease
Pulmonary Arterial Hypertension (PAH) is a severe complication of Connective Tissue Disease (CTD), with remarkable morbidity and mortality. However, the molecular and genetic basis of CTD-PAH remains incompletely understood. This study aimed to screen for genetic defects in a cohort of patients with...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231632/ https://www.ncbi.nlm.nih.gov/pubmed/34199176 http://dx.doi.org/10.3390/cells10061488 |
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author | Hernandez-Gonzalez, Ignacio Tenorio-Castano, Jair Ochoa-Parra, Nuria Gallego, Natalia Pérez-Olivares, Carmen Lago-Docampo, Mauro Palomino Doza, Julian Valverde, Diana Lapunzina, Pablo Escribano-Subias, Pilar |
author_facet | Hernandez-Gonzalez, Ignacio Tenorio-Castano, Jair Ochoa-Parra, Nuria Gallego, Natalia Pérez-Olivares, Carmen Lago-Docampo, Mauro Palomino Doza, Julian Valverde, Diana Lapunzina, Pablo Escribano-Subias, Pilar |
author_sort | Hernandez-Gonzalez, Ignacio |
collection | PubMed |
description | Pulmonary Arterial Hypertension (PAH) is a severe complication of Connective Tissue Disease (CTD), with remarkable morbidity and mortality. However, the molecular and genetic basis of CTD-PAH remains incompletely understood. This study aimed to screen for genetic defects in a cohort of patients with CTD-PAH, using a PAH-specific panel of 35 genes. During recruitment, 79 patients were studied, including 59 Systemic Sclerosis patients (SSc) and 69 females. Disease-associated variants were observed in nine patients: 4 pathogenic/likely pathogenic variants in 4 different genes (TBX4, ABCC8, KCNA5 and GDF2/BMP9) and 5 Variants of Unknown Significance (VUS) in 4 genes (ABCC8, NOTCH3, TOPBP1 and CTCFL). One patient with mixed CTD had a frameshift pathogenic variant in TBX4. Two patients with SSc-PAH carried variants in ABCC8. A patient diagnosed with Systemic Lupus Erythematous (SLE) presented a pathogenic nonsense variant in GDF2/BMP9. Another patient with SSc-PAH presented a pathogenic variant in KCNA5. Four patients with SSc-PAH carried a VUS in NOTCH1, CTCFL, CTCFL and TOPBP1, respectively. These findings suggest that genetic factors may contribute to Pulmonary Vascular Disease (PVD) in CTD patients. |
format | Online Article Text |
id | pubmed-8231632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82316322021-06-26 Novel Genetic and Molecular Pathways in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease Hernandez-Gonzalez, Ignacio Tenorio-Castano, Jair Ochoa-Parra, Nuria Gallego, Natalia Pérez-Olivares, Carmen Lago-Docampo, Mauro Palomino Doza, Julian Valverde, Diana Lapunzina, Pablo Escribano-Subias, Pilar Cells Brief Report Pulmonary Arterial Hypertension (PAH) is a severe complication of Connective Tissue Disease (CTD), with remarkable morbidity and mortality. However, the molecular and genetic basis of CTD-PAH remains incompletely understood. This study aimed to screen for genetic defects in a cohort of patients with CTD-PAH, using a PAH-specific panel of 35 genes. During recruitment, 79 patients were studied, including 59 Systemic Sclerosis patients (SSc) and 69 females. Disease-associated variants were observed in nine patients: 4 pathogenic/likely pathogenic variants in 4 different genes (TBX4, ABCC8, KCNA5 and GDF2/BMP9) and 5 Variants of Unknown Significance (VUS) in 4 genes (ABCC8, NOTCH3, TOPBP1 and CTCFL). One patient with mixed CTD had a frameshift pathogenic variant in TBX4. Two patients with SSc-PAH carried variants in ABCC8. A patient diagnosed with Systemic Lupus Erythematous (SLE) presented a pathogenic nonsense variant in GDF2/BMP9. Another patient with SSc-PAH presented a pathogenic variant in KCNA5. Four patients with SSc-PAH carried a VUS in NOTCH1, CTCFL, CTCFL and TOPBP1, respectively. These findings suggest that genetic factors may contribute to Pulmonary Vascular Disease (PVD) in CTD patients. MDPI 2021-06-13 /pmc/articles/PMC8231632/ /pubmed/34199176 http://dx.doi.org/10.3390/cells10061488 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brief Report Hernandez-Gonzalez, Ignacio Tenorio-Castano, Jair Ochoa-Parra, Nuria Gallego, Natalia Pérez-Olivares, Carmen Lago-Docampo, Mauro Palomino Doza, Julian Valverde, Diana Lapunzina, Pablo Escribano-Subias, Pilar Novel Genetic and Molecular Pathways in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease |
title | Novel Genetic and Molecular Pathways in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease |
title_full | Novel Genetic and Molecular Pathways in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease |
title_fullStr | Novel Genetic and Molecular Pathways in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease |
title_full_unstemmed | Novel Genetic and Molecular Pathways in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease |
title_short | Novel Genetic and Molecular Pathways in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease |
title_sort | novel genetic and molecular pathways in pulmonary arterial hypertension associated with connective tissue disease |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231632/ https://www.ncbi.nlm.nih.gov/pubmed/34199176 http://dx.doi.org/10.3390/cells10061488 |
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