FRI157 Systematic Germline Genetic Analysis In A Cohort Of Adults With Primary Aldosteronism And Hypertension Onset ≤35 yo : Low Yield Of Genetic Pathogenic Variants
Notice bibliographique
Résumé
Abstract Disclosure: S. Parisien-La Salle: None. D. Nadine: None. Z. El-Haffaf: None. A. Lacroix: None. I. Bourdeau: None. Introduction: Primary aldosteronism (PA) is a common but underdiagnosed cause of hypertension. Although most cases are sporadic, up to 5% of patients have a familial form of PA. Current guidelines recommend germline genetic analysis in patients who present PA < 20 yo or have a family history of PA. As PA is underdiagnosed, we hypothesized that some patients with PA do not undergo germline genetic screening since familial history of PA is unrecognized. Objective: To evaluate the yield of systematic germline genetic analysis for familial PA in patients with PA, hypertension detection ≤ 35 yo and a family history of hypertension. Methods: From 2012-2022, patients diagnosed with PA (positive ARR and confirmatory testing), hypertension onset ≤ 35 yo and a family history of hypertension were offered genetic counselling for germline screening for known familial causes of PA. After informed consent, patients underwent germline analysis for the chimeric gene CYP11B2/CYP11B1 (Ruhr University Bochum, Germany) and a multigene panel including KCNJ5, CACNA1D, CACNA1H and CLCN2 genes (Fulgent, CA). Results: Twenty-five patients consented for genetic analysis. Thirteen patients (52%) were female. In regards to ethnic origin, 52% were French Canadians, 24% African-Americans and the other 24% was split between Asian, European and Middle Eastern descent. The mean age at diagnosis of hypertension was 28.3 yo and 39.7 yo at PA diagnosis. At PA diagnosis, 91.3% (21/23) had previous hypokalemia and 12% (3/25) a cortisol co-secretion (1 mg dexamethasone test> 50 nmol/L). Approximately 13% were on one hypertension drug, 30% on two, 26% on three, 26% on four and 5% were on five medications. Comobordities included: 8% atrial fibrillation, 20% obstructive sleep apnea and 4% coronary heart disease. All patients had a family history of hypertension, 5 patients (20%) had a family history of stroke, and 1 patient (4%) had a family history of PA. Of the patients who had already undergone adrenal vein sampling (n=22), 68.2% (15/22) underwent an adrenalectomy for lateralised aldosterone secretion and 31.8% (7/22) were treated with medical therapy for bilateral disease. None of the 24 patients who underwent testing for glucocorticoid-remediable aldosteronism were found to have the chimeric gene CYP11B2/CYP11B1. Twenty-three patients underwent the multigene panel and no pathogenic variants were identified. However, 4/23 (17,4%) patients carried a variant of unknown significance (VUS) in CACNA1H or CLCN2 genes (CACNA1H c.1315C>T(p.Arg439Cys),CACNA1H c.3868G>A(p.Val1290Ile),CACNA1H c.1939G>A (p.Gly647Ser), CLCN2 c.2402C>T, (p.Thr801Ile)). Conclusion: Systematic germline genetic testing for familial PA in this cohort of patients with PA, hypertension diagnosis ≤ 35 yo and a family history of hypertension did not yield positive results. Although PA is an underdiagnosed disease, familial forms remain very rare. Presentation: Friday, June 16, 2023
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».