{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:10:23Z","timestamp":1777950623577,"version":"3.51.4"},"reference-count":29,"publisher":"King Faisal Specialist Hospital and Research Centre","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ann Saudi Med"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Pulmonary arterial hypertension (PAH) involves progressive obstruction of small pulmonary vessels due to vascular remodeling. Although the genetic architecture of PAH is increasingly understood, it remains poorly characterized in Algeria due to limited studies and the absence of molecular diagnostic infrastructure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>OBJECTIVES:<\/jats:title>\n                    <jats:p>\n                      To identify pathogenic variants in\n                      <jats:italic toggle=\"yes\">BMPR2<\/jats:italic>\n                      and other PAH-related genes in Algerian patients, enabling targeted screening of high-risk individuals, refined classification of variants of uncertain significance (VUS), and early, personalized clinical management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DESIGN:<\/jats:title>\n                    <jats:p>Cross-sectional study using targeted next-generation sequencing (NGS) of 15 PAH-associated genes<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SETTING:<\/jats:title>\n                    <jats:p>Multicenter (3 university hospitals in Algiers)<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS:<\/jats:title>\n                    <jats:p>Thirty adults with confirmed pre-capillary PAH (Group 1) of unknown etiology, diagnosed according to clinical guidelines, and 30 age- and sex-matched healthy controls were enrolled. Peripheral blood was collected for genetic analysis, and pathogenic variants were identified using targeted NGS. IL-6 plasma levels were quantified by immunoassay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN OUTCOME MEASURES:<\/jats:title>\n                    <jats:p>Contribution to the genetic characterization of PAH and potential implications for personalized clinical management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SAMPLE SIZE:<\/jats:title>\n                    <jats:p>30 patients and 30 controls<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Pathogenic variants were identified in 6 out of 30 patients (20%) involving\n                      <jats:italic toggle=\"yes\">BMPR2, SOX17, TBX4, ATP13A3<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">EIF2AK4<\/jats:italic>\n                      . Homozygosity for the\n                      <jats:italic toggle=\"yes\">EIF2AK4<\/jats:italic>\n                      variant led to a revised diagnosis of Pulmonary Veno-Occlusive Disease\/Pulmonary Capillary Hemangiomatosis (PVOD\/PCH). Carriers of pathogenic variants were younger at diagnosis (30 vs. 49 years,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =.0115) and exhibited more severe hemodynamic profiles. Most patients (80%) were in New York Heart Association (NYHA) functional class III or IV. Mean pulmonary arterial pressure (mPAP) was 59 (45\u201364) vs. 46 (39.7\u201359) mmHg in patients without variants. IL-6 levels were significantly higher in patients than in controls (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION:<\/jats:title>\n                    <jats:p>This first genetic study in Algerian PAH patients highlights the relevance of genetic testing for diagnosis and management. The findings support the development of national genetic infrastructure and confirm the role of inflammation in PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS:<\/jats:title>\n                    <jats:p>Modest sample size and the lack of family segregation data limited the assessment of Variant of Unknown Significance (VUS) and heritability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.5144\/0256-4947.2026.111","type":"journal-article","created":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T07:54:12Z","timestamp":1776585252000},"page":"111-120","source":"Crossref","is-referenced-by-count":0,"title":["Genetic analysis and clinical phenotype of pulmonary arterial hypertension in an Algerian population"],"prefix":"10.5144","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4073-4932","authenticated-orcid":false,"given":"Amel Wafa","family":"Berkane","sequence":"first","affiliation":[{"name":"From the Section of Endocrinology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumedienne, Bab Ezzouar, Algiers, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachida","family":"Yahiaoui","sequence":"additional","affiliation":[{"name":"From the Department of Pulmonology, Faculty of Medicine, University of Algiers 1, Issad Hassani Hospital, Beni Messous, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nad\u00e9ra","family":"Methia","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Faculty of Medicine, University of Algiers 1, Mustapha Bacha Hospital, Algiers, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nassima","family":"Djami-Temim","sequence":"additional","affiliation":[{"name":"From the Department of Pulmonology, Faculty of Medicine, University of Algiers 1, Mohammed Lamine Debaghine Hospital, Bab El Oued, Algiers, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florence","family":"Coulet","sequence":"additional","affiliation":[{"name":"From the Department of Genetics, Piti\u00e9-Salp\u00eatri\u00e8re University Hospital, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrice","family":"Antigny","sequence":"additional","affiliation":[{"name":"From the Universite Paris-Saclay, INSERM_S HPPIT, AP HP, Department of Respiratory and Intensive Care Medicine (FHU Cournand, ERN-LUNG), Marie Lannelongue Hospital and Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Montani","sequence":"additional","affiliation":[{"name":"From the Universite Paris-Saclay, INSERM_S HPPIT, AP HP, Department of Respiratory and Intensive Care Medicine (FHU Cournand, ERN-LUNG), Marie Lannelongue Hospital and Bic\u00eatre Hospital, Le Kremlin-Bic\u00eatre, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zohra","family":"Hamouli-Said","sequence":"additional","affiliation":[{"name":"From the Section of Endocrinology, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumedienne, Bab Ezzouar, Algiers, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3134","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.banm.2022.10.009"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac237"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01324-2024"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01887-2018"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01032-2015"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03672-4"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.321554"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00442-2024"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2018.12.001"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01471-2022"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0001-4079(19)30470-4"},{"issue":"2","key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.14797\/ZOQM5771","article-title":"Genetic counseling and testing in pulmonary arterial hypertension","volume":"17","author":"Elliott CG","year":"2021","unstructured":"Elliott CG. 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