Genetic screening in heritable thoracic aortic disease—rationale, potentials and pitfalls

Acharya, Metesh; Maselli, Daniele; Mariscalco, Giovanni

doi:10.1007/s12055-020-01124-7

Cited by 6 publications

(9 citation statements)

References 58 publications

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“…Genetics constitute a pivotal element in the pathogenesis of thoracic aortic aneurysm and dissection (TAAD), a potentially life-threatening condition characterized by the debilitation of the aortic wall, predisposing it to dilation, aneurysm formation, and the ominous prospects of dissection or rupture [ 7 , 8 ]. Inherited connective tissue disorders substantially augment the risk of AD.…”

Section: Reviewmentioning

confidence: 99%

“…For instance, mutations affecting genes encoding constituents of the extracellular matrix, such as FBN1, FBN2, COL3A1, and ELN, have the propensity to disrupt the structural robustness of the aortic wall, consequently fostering weakening and dilation. Correspondingly, mutations impacting vascular smooth muscle cell contractility, including MYH11, ACTA2, and MYLK, can impede the contractile efficacy of smooth muscle cells, thereby engendering dysfunction in the aortic wall and predisposing individuals to dissection [ 8 , 10 , 11 ]. Moreover, genetic aberrations concerning the transforming growth factor-ß (TGF-ß) signaling pathway, such as mutations in TGFBR1, TGFBR2, and SMAD genes, have been implicated in the pathogenesis of AD.…”

Section: Reviewmentioning

confidence: 99%

“…Syndromic forms, constituting a minority of TAAD cases, are typified by the involvement of extra-aortic organ systems and are often affiliated with well-defined genetic syndromes, such as Marfan syndrome and Loeys-Dietz syndrome. In contradistinction, non-syndromic forms encompass the preponderance of TAAD cases and are primarily confined to the aorta, devoid of overt involvement of other organ systems [ 7 , 8 ].…”

Section: Reviewmentioning

confidence: 99%

“…By discerning specific genetic mutations correlated with TAAD, genetic screening aids in stratifying patients based on their vulnerability to developing AD. Furthermore, genetic testing facilitates the premature detection of TAAD in asymptomatic individuals with a familial history of the condition, thereby enabling timely intervention and prophylactic measures [ 8 ]. The American College of Cardiology/American Heart Association proffers recommendations for genetic counseling and testing for first-degree relatives of patients harboring known genetic mutations associated with TAAD, such as FBN1, TGFBR1, TGFBR2, COL3A1, ACTA2, and MYH11 [ 8 , 12 ].…”

Section: Reviewmentioning

confidence: 99%

“…Furthermore, genetic testing facilitates the premature detection of TAAD in asymptomatic individuals with a familial history of the condition, thereby enabling timely intervention and prophylactic measures [ 8 ]. The American College of Cardiology/American Heart Association proffers recommendations for genetic counseling and testing for first-degree relatives of patients harboring known genetic mutations associated with TAAD, such as FBN1, TGFBR1, TGFBR2, COL3A1, ACTA2, and MYH11 [ 8 , 12 ]. Additionally, sequencing of other genes may be contemplated in patients with a familial history of TAAD and clinical manifestations evocative of specific genetic mutations.…”

Section: Reviewmentioning

confidence: 99%

See 4 more Smart Citations

Unraveling the Enigma of Aortic Dissection: From Genetics to Innovative Therapies

Godugu,

Sinha,

Pradeepan

et al. 2024

Cureus

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Aortic dissection (AD) presents a critical medical emergency characterized by a tear in the aortic wall, necessitating prompt recognition and management to mitigate catastrophic complications. Despite advancements in medical technology and therapeutic interventions, AD remains a formidable challenge, often resulting in severe morbidity and mortality. This narrative review provides a comprehensive overview of AD, encompassing its clinical presentation, diagnostic modalities, and management strategies, while also exploring emerging trends and innovations in its management. Genetic predispositions significantly influence AD pathogenesis, with over 30 contributory genes identified, emphasizing the importance of genetic screening and counseling. Classification systems such as Stanford and DeBakey, alongside their revised counterparts, aid in categorizing AD and guiding treatment decisions. Advancements in diagnostic imaging, including transesophageal echocardiography and computed tomography angiography, have enhanced diagnostic precision, augmented by artificial intelligence and machine learning algorithms. Pharmacological innovations focus on optimizing medical therapy, while surgical and endovascular approaches offer minimally invasive treatment options. Hybrid procedures and aortic valve-sparing techniques broaden treatment avenues, while bioresorbable stent grafts hold promise for tissue regeneration. Collaborative efforts and ongoing research are essential to address remaining challenges and improve outcomes in managing AD. This review contributes to the understanding of AD's complexity and facilitates informed decision-making in clinical practice, underscoring the imperative for continued innovation and research in AD management.

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

See 3 more Smart Citations

Unraveling the Enigma of Aortic Dissection: From Genetics to Innovative Therapies

Godugu,

Sinha,

Pradeepan

et al. 2024

Cureus

View full text Add to dashboard Cite

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Practice Patterns and Barriers to Vascular Genetic Testing Among Vascular Surgeons

Dittman,

Prakash,

Gupta

et al. 2024

Annals of Vascular Surgery

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Contributions of Germline and Somatic Mosaic Genetics to Thoracic Aortic Aneurysms in Nonsyndromic Individuals

Chen,

Deng,

Yamada

et al. 2024

JAHA

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Background Thoracic aortic aneurysm (TAA) is associated with significant morbidity and mortality. Although individuals with family histories of TAA often undergo clinical molecular genetic testing, adults with nonsyndromic TAA are not typically evaluated for genetic causes. We sought to understand the genetic contribution of both germline and somatic mosaic variants in a cohort of adult individuals with nonsyndromic TAA at a single center. Methods and Results One hundred eighty‐one consecutive patients <60 years who presented with nonsyndromic TAA at the Massachusetts General Hospital underwent deep (>500×) targeted sequencing across 114 candidate genes associated with TAA and its related functional pathways. Samples from 354 age‐ and sex‐matched individuals without TAA were also sequenced, with a 2:1 matching. We found significant enrichments for germline (odds ratio [OR], 2.44, P =4.6×10 −6 [95% CI, 1.67–3.58]) and also somatic mosaic variants (OR, 4.71, P =0.026 [95% CI, 1.20–18.43]) between individuals with and without TAA. Likely genetic causes were present in 24% with nonsyndromic TAA, of which 21% arose from germline variants and 3% from somatic mosaic alleles. The 3 most frequently mutated genes in our cohort were FLNA (encoding Filamin A), NOTCH3 (encoding Notch receptor 3), and FBN1 (encoding Fibrillin‐1). There was increased frequency of both missense and loss of function variants in TAA individuals. Conclusions Likely contributory dominant acting genetic variants were found in almost one quarter of nonsyndromic adults with TAA. Our findings suggest a more extensive genetic architecture to TAA than expected and that genetic testing may improve the care and clinical management of adults with nonsyndromic TAA.

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Genetic screening in heritable thoracic aortic disease—rationale, potentials and pitfalls

Cited by 6 publications

References 58 publications

Unraveling the Enigma of Aortic Dissection: From Genetics to Innovative Therapies

Unraveling the Enigma of Aortic Dissection: From Genetics to Innovative Therapies

Practice Patterns and Barriers to Vascular Genetic Testing Among Vascular Surgeons

Contributions of Germline and Somatic Mosaic Genetics to Thoracic Aortic Aneurysms in Nonsyndromic Individuals

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