Expanding the Evidence of a Semi-Dominant Inheritance in <i>GDF2</i> Associated with Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) sometimes co-exists with hereditary hemorrhagic telangiectasia (HHT). Despite being clinically diagnosable according to Curaçao criteria, HHT can be difficult to diagnose due to its clinically heterogenicity and highly overlapping with PAH. Genetic analysis of t...
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2021
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oai:doaj.org-article:bfd329b4eb8144be978a1d00ff7e1e522021-11-25T17:12:23ZExpanding the Evidence of a Semi-Dominant Inheritance in <i>GDF2</i> Associated with Pulmonary Arterial Hypertension10.3390/cells101131782073-4409https://doaj.org/article/bfd329b4eb8144be978a1d00ff7e1e522021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3178https://doaj.org/toc/2073-4409Pulmonary arterial hypertension (PAH) sometimes co-exists with hereditary hemorrhagic telangiectasia (HHT). Despite being clinically diagnosable according to Curaçao criteria, HHT can be difficult to diagnose due to its clinically heterogenicity and highly overlapping with PAH. Genetic analysis of the associated genes <i>ACVRL1</i>, <i>ENG</i>, <i>SMAD4</i> and <i>GDF2</i> can help to confirm or discard the presumptive diagnosis. As part of the clinical routine and to establish a genetic diagnosis, we have analyzed a cohort of patients with PAH and overlapping HHT features through a customized Next Generation Sequencing (NGS) panel of 21 genes, designed and validated in-house. We detected a homozygous missense variant in <i>GDF2</i> in a pediatric patient diagnosed with PAH associated with HHT and a missense variant along with a heterozygous deletion in another idiopathic PAH patient (compound heterozygous inheritance). In order to establish variant segregation, we analyzed all available family members. In both cases, parents were carriers for the variants, but neither was affected. Our results expand the clinical spectrum and the inheritance pattern associated with <i>GDF2</i> pathogenic variants suggesting incomplete penetrance and/or variability of expressivity with a semi-dominant pattern of inheritance.Natalia GallegoAlejandro Cruz-UtrillaInmaculada GuillénAmparo Moya BonoraNuria OchoaPedro AriasPablo LapunzinaPilar Escribano-SubiasJulián NevadoJair Tenorio-CastañoMDPI AGarticle<i>GDF2</i>hereditary hemorrhagic telangiectasiapulmonary arterial hypertensionmassive parallel sequencingNGSgenomic medicineBiology (General)QH301-705.5ENCells, Vol 10, Iss 3178, p 3178 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
<i>GDF2</i> hereditary hemorrhagic telangiectasia pulmonary arterial hypertension massive parallel sequencing NGS genomic medicine Biology (General) QH301-705.5 |
| spellingShingle |
<i>GDF2</i> hereditary hemorrhagic telangiectasia pulmonary arterial hypertension massive parallel sequencing NGS genomic medicine Biology (General) QH301-705.5 Natalia Gallego Alejandro Cruz-Utrilla Inmaculada Guillén Amparo Moya Bonora Nuria Ochoa Pedro Arias Pablo Lapunzina Pilar Escribano-Subias Julián Nevado Jair Tenorio-Castaño Expanding the Evidence of a Semi-Dominant Inheritance in <i>GDF2</i> Associated with Pulmonary Arterial Hypertension |
| description |
Pulmonary arterial hypertension (PAH) sometimes co-exists with hereditary hemorrhagic telangiectasia (HHT). Despite being clinically diagnosable according to Curaçao criteria, HHT can be difficult to diagnose due to its clinically heterogenicity and highly overlapping with PAH. Genetic analysis of the associated genes <i>ACVRL1</i>, <i>ENG</i>, <i>SMAD4</i> and <i>GDF2</i> can help to confirm or discard the presumptive diagnosis. As part of the clinical routine and to establish a genetic diagnosis, we have analyzed a cohort of patients with PAH and overlapping HHT features through a customized Next Generation Sequencing (NGS) panel of 21 genes, designed and validated in-house. We detected a homozygous missense variant in <i>GDF2</i> in a pediatric patient diagnosed with PAH associated with HHT and a missense variant along with a heterozygous deletion in another idiopathic PAH patient (compound heterozygous inheritance). In order to establish variant segregation, we analyzed all available family members. In both cases, parents were carriers for the variants, but neither was affected. Our results expand the clinical spectrum and the inheritance pattern associated with <i>GDF2</i> pathogenic variants suggesting incomplete penetrance and/or variability of expressivity with a semi-dominant pattern of inheritance. |
| format |
article |
| author |
Natalia Gallego Alejandro Cruz-Utrilla Inmaculada Guillén Amparo Moya Bonora Nuria Ochoa Pedro Arias Pablo Lapunzina Pilar Escribano-Subias Julián Nevado Jair Tenorio-Castaño |
| author_facet |
Natalia Gallego Alejandro Cruz-Utrilla Inmaculada Guillén Amparo Moya Bonora Nuria Ochoa Pedro Arias Pablo Lapunzina Pilar Escribano-Subias Julián Nevado Jair Tenorio-Castaño |
| author_sort |
Natalia Gallego |
| title |
Expanding the Evidence of a Semi-Dominant Inheritance in <i>GDF2</i> Associated with Pulmonary Arterial Hypertension |
| title_short |
Expanding the Evidence of a Semi-Dominant Inheritance in <i>GDF2</i> Associated with Pulmonary Arterial Hypertension |
| title_full |
Expanding the Evidence of a Semi-Dominant Inheritance in <i>GDF2</i> Associated with Pulmonary Arterial Hypertension |
| title_fullStr |
Expanding the Evidence of a Semi-Dominant Inheritance in <i>GDF2</i> Associated with Pulmonary Arterial Hypertension |
| title_full_unstemmed |
Expanding the Evidence of a Semi-Dominant Inheritance in <i>GDF2</i> Associated with Pulmonary Arterial Hypertension |
| title_sort |
expanding the evidence of a semi-dominant inheritance in <i>gdf2</i> associated with pulmonary arterial hypertension |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/bfd329b4eb8144be978a1d00ff7e1e52 |
| work_keys_str_mv |
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