An emerging phenotype of pulmonary arterial hypertension patients carrying SOX17 variants
Copyright ©The authors 2022..
BACKGROUND: The phenotype of pulmonary arterial hypertension (PAH) patients carrying SOX17 pathogenic variants remains mostly unknown.
METHODS: We report the genetic analysis findings, characteristics and outcomes of patients with heritable PAH carrying SOX17 variants from the French Pulmonary Hypertension Network.
RESULTS: 20 patients and eight unaffected relatives were identified. The median (range) age at diagnosis was 17 (2-53) years, with a female:male ratio of 1.5. At diagnosis, most of the patients (74%) were in New York Heart Association Functional Class III or IV with severe haemodynamic compromise, including a median pulmonary vascular resistance of 14.0 (4.2-31.5) WU. An associated congenital heart disease (CHD) was found in seven PAH patients (35%). Patients with CHD-associated PAH were significantly younger at diagnosis than PAH patients without CHD. Four patients (20%) suffered from recurrent haemoptysis requiring repeated arterial embolisations. 13 out of 16 patients (81%) for whom imaging was available displayed chest computed tomography abnormalities, including dilated, tortuous pulmonary vessels, ground-glass opacities as well as anomalies of the bronchial and nonbronchial arteries. After a median (range) follow-up of 47 (1-591) months, 10 patients underwent lung transplantation and one patient benefited from a heart-lung transplantation due to associated CHD. Histopathological analysis of lung explants showed a congested lung architecture with severe pulmonary arterial remodelling, subpleural vessel dilation and numerous haemorrhagic foci.
CONCLUSIONS: PAH due to SOX17 pathogenic variants is a severe phenotype, frequently associated with CHD, haemoptysis and radiological abnormalities. Pathological assessment reveals severe pulmonary arterial remodelling and malformations affecting pulmonary vessels and thoracic systemic arteries.
| Errataetall: | |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:60 |
|---|---|
| Enthalten in: |
The European respiratory journal - 60(2022), 6 vom: 26. Dez. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Montani, David [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Journal Article |
|---|
| Anmerkungen: |
Date Completed 01.09.2023 Date Revised 18.09.2023 published: Electronic-Print CommentIn: Eur Respir J. 2022 Dec 8;60(6):. - PMID 37651375 Citation Status MEDLINE |
|---|
| doi: |
10.1183/13993003.00656-2022 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM341406120 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM341406120 | ||
| 003 | DE-627 | ||
| 005 | 20231226011712.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1183/13993003.00656-2022 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1137.xml |
| 035 | |a (DE-627)NLM341406120 | ||
| 035 | |a (NLM)35618278 | ||
| 035 | |a (PII)2200656 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Montani, David |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An emerging phenotype of pulmonary arterial hypertension patients carrying SOX17 variants |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.09.2023 | ||
| 500 | |a Date Revised 18.09.2023 | ||
| 500 | |a published: Electronic-Print | ||
| 500 | |a CommentIn: Eur Respir J. 2022 Dec 8;60(6):. - PMID 37651375 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright ©The authors 2022. | ||
| 520 | |a BACKGROUND: The phenotype of pulmonary arterial hypertension (PAH) patients carrying SOX17 pathogenic variants remains mostly unknown | ||
| 520 | |a METHODS: We report the genetic analysis findings, characteristics and outcomes of patients with heritable PAH carrying SOX17 variants from the French Pulmonary Hypertension Network | ||
| 520 | |a RESULTS: 20 patients and eight unaffected relatives were identified. The median (range) age at diagnosis was 17 (2-53) years, with a female:male ratio of 1.5. At diagnosis, most of the patients (74%) were in New York Heart Association Functional Class III or IV with severe haemodynamic compromise, including a median pulmonary vascular resistance of 14.0 (4.2-31.5) WU. An associated congenital heart disease (CHD) was found in seven PAH patients (35%). Patients with CHD-associated PAH were significantly younger at diagnosis than PAH patients without CHD. Four patients (20%) suffered from recurrent haemoptysis requiring repeated arterial embolisations. 13 out of 16 patients (81%) for whom imaging was available displayed chest computed tomography abnormalities, including dilated, tortuous pulmonary vessels, ground-glass opacities as well as anomalies of the bronchial and nonbronchial arteries. After a median (range) follow-up of 47 (1-591) months, 10 patients underwent lung transplantation and one patient benefited from a heart-lung transplantation due to associated CHD. Histopathological analysis of lung explants showed a congested lung architecture with severe pulmonary arterial remodelling, subpleural vessel dilation and numerous haemorrhagic foci | ||
| 520 | |a CONCLUSIONS: PAH due to SOX17 pathogenic variants is a severe phenotype, frequently associated with CHD, haemoptysis and radiological abnormalities. Pathological assessment reveals severe pulmonary arterial remodelling and malformations affecting pulmonary vessels and thoracic systemic arteries | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a SOX17 protein, human |2 NLM | |
| 650 | 7 | |a SOXF Transcription Factors |2 NLM | |
| 700 | 1 | |a Lechartier, Benoit |e verfasserin |4 aut | |
| 700 | 1 | |a Girerd, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Eyries, Mélanie |e verfasserin |4 aut | |
| 700 | 1 | |a Ghigna, Maria-Rosa |e verfasserin |4 aut | |
| 700 | 1 | |a Savale, Laurent |e verfasserin |4 aut | |
| 700 | 1 | |a Jaïs, Xavier |e verfasserin |4 aut | |
| 700 | 1 | |a Seferian, Andrei |e verfasserin |4 aut | |
| 700 | 1 | |a Jevnikar, Mitja |e verfasserin |4 aut | |
| 700 | 1 | |a Boucly, Athénais |e verfasserin |4 aut | |
| 700 | 1 | |a Riou, Marianne |e verfasserin |4 aut | |
| 700 | 1 | |a Traclet, Julie |e verfasserin |4 aut | |
| 700 | 1 | |a Chaouat, Ari |e verfasserin |4 aut | |
| 700 | 1 | |a Levy, Maryline |e verfasserin |4 aut | |
| 700 | 1 | |a Le Pavec, Jerome |e verfasserin |4 aut | |
| 700 | 1 | |a Fadel, Elie |e verfasserin |4 aut | |
| 700 | 1 | |a Perros, Frédéric |e verfasserin |4 aut | |
| 700 | 1 | |a Soubrier, Florent |e verfasserin |4 aut | |
| 700 | 1 | |a Remy-Jardin, Martine |e verfasserin |4 aut | |
| 700 | 1 | |a Sitbon, Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Bonnet, Damien |e verfasserin |4 aut | |
| 700 | 1 | |a Humbert, Marc |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The European respiratory journal |d 1989 |g 60(2022), 6 vom: 26. Dez. |w (DE-627)NLM012664782 |x 0903-1936 |7 nnns |
| 773 | 1 | 8 | |g volume:60 |g year:2022 |g number:6 |g day:26 |g month:12 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1183/13993003.00656-2022 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 60 |j 2022 |e 6 |b 26 |c 12 | ||