4 results on '"Gornik, Heather L."'
Search Results
2. Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia.
- Author
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Persu, Alexandre, Dobrowolski, Piotr, Gornik, Heather L, Olin, Jeffrey W, Adlam, David, Azizi, Michel, Boutouyrie, Pierre, Bruno, Rosa Maria, Boulanger, Marion, Demoulin, Jean-Baptiste, Ganesh, Santhi K, Guzik, Tomasz J., Januszewicz, Magdalena, Kovacic, Jason C, Kruk, Mariusz, Leeuw, Peter de, Loeys, Bart L, Pappaccogli, Marco, Perik, Melanie H A M, and Touzé, Emmanuel
- Subjects
DYSPLASIA ,ARTERIAL diseases ,GENETICS ,RENAL artery ,SYMPTOMS ,FIBRODYSPLASIA ossificans progressiva - Abstract
Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease's clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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- View/download PDF
3. Rare loss-of-function mutations of PTGIR are enriched in fibromuscular dysplasia
- Author
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Georges, Adrien, primary, Albuisson, Juliette, additional, Berrandou, Takiy, additional, Dupré, Délia, additional, Lorthioir, Aurélien, additional, D’Escamard, Valentina, additional, Di Narzo, Antonio F, additional, Kadian-Dodov, Daniella, additional, Olin, Jeffrey W, additional, Warchol-Celinska, Ewa, additional, Prejbisz, Aleksander, additional, Januszewicz, Andrzej, additional, Bruneval, Patrick, additional, Baranowska, Anna A, additional, Webb, Tom R, additional, Hamby, Stephen E, additional, Samani, Nilesh J, additional, Adlam, David, additional, Fendrikova-Mahlay, Natalia, additional, Hazen, Stanley, additional, Wang, Yu, additional, Yang, Min-Lee, additional, Hunker, Kristina, additional, Combaret, Nicolas, additional, Motreff, Pascal, additional, Chédid, Antoine, additional, Fiquet, Béatrice, additional, Plouin, Pierre-François, additional, Mousseaux, Elie, additional, Azarine, Arshid, additional, Amar, Laurence, additional, Azizi, Michel, additional, Gornik, Heather L, additional, Ganesh, Santhi K, additional, Kovacic, Jason C, additional, Jeunemaitre, Xavier, additional, and Bouatia-Naji, Nabila, additional
- Published
- 2020
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4. Rare loss-of-function mutations of PTGIR are enriched in fibromuscular dysplasia.
- Author
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Georges A, Albuisson J, Berrandou T, Dupré D, Lorthioir A, D'Escamard V, Di Narzo AF, Kadian-Dodov D, Olin JW, Warchol-Celinska E, Prejbisz A, Januszewicz A, Bruneval P, Baranowska AA, Webb TR, Hamby SE, Samani NJ, Adlam D, Fendrikova-Mahlay N, Hazen S, Wang Y, Yang ML, Hunker K, Combaret N, Motreff P, Chédid A, Fiquet B, Plouin PF, Mousseaux E, Azarine A, Amar L, Azizi M, Gornik HL, Ganesh SK, Kovacic JC, Jeunemaitre X, and Bouatia-Naji N
- Subjects
- Adult, Aged, Australia, Coronary Vessel Anomalies diagnosis, Coronary Vessel Anomalies metabolism, DNA Mutational Analysis, Databases, Genetic, Europe, Female, Fibromuscular Dysplasia diagnosis, Fibromuscular Dysplasia metabolism, Genetic Predisposition to Disease, HEK293 Cells, Humans, Male, Middle Aged, Phenotype, Predictive Value of Tests, Receptors, Epoprostenol metabolism, Risk Assessment, Risk Factors, United States, Vascular Diseases diagnosis, Vascular Diseases genetics, Vascular Diseases metabolism, Coronary Vessel Anomalies genetics, Fibromuscular Dysplasia genetics, Loss of Function Mutation, Mutation, Missense, Receptors, Epoprostenol genetics, Vascular Diseases congenital
- Abstract
Aims: Fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. We aimed to identify rare genetic causes to elucidate molecular mechanisms implicated in FMD and SCAD., Methods and Results: We analysed 29 exomes that included familial and sporadic FMD. We identified one rare loss-of-function variant (LoF) (frequencygnomAD = 0.000075) shared by two FMD sisters in the prostaglandin I2 receptor gene (PTGIR), a key player in vascular remodelling. Follow-up was conducted by targeted or Sanger sequencing (1071 FMD and 363 SCAD patients) or lookups in exome (264 FMD) or genome sequences (480 SCAD), all independent and unrelated. It revealed four additional LoF allele carriers, in addition to several rare missense variants, among FMD patients, and two LoF allele carriers among SCAD patients, including one carrying a rare splicing mutation (c.768 + 1C>G). We used burden test to test for enrichment in patients compared to gnomAD controls, which detected a putative enrichment in FMD (PTRAPD = 8 × 10-4), but not a significant enrichment (PTRAPD = 0.12) in SCAD. The biological effects of variants on human prostaclycin receptor (hIP) signalling and protein expression were characterized using transient overexpression in human cells. We confirmed the LoFs (Q163X and P17RfsX6) and one missense (L67P), identified in one FMD and one SCAD patient, to severely impair hIP function in vitro., Conclusions: Our study shows that rare genetic mutations in PTGIR are enriched among FMD patients and found in SCAD patients, suggesting a role for prostacyclin signalling in non-atherosclerotic stenosis and dissection., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)
- Published
- 2021
- Full Text
- View/download PDF
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