The Genetics of Aortopathies in Clinical Cardiology

Goyal, Amit; Keramati, Ali R.; Czarny, Matthew J.; Resar, Jon R.; Mani, Arya

doi:10.1177/1179546817709787

Cited by 38 publications

(38 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The examined population in the first phase of the genetic testing consisted of 19 men (33%) and 38 women (67%) with an average age of 33 (30)(31)(32)(33)(34)(35)(36)(37) years at the time of the genetic screening. Their median systemic score was 8 (ranging from 7 to 10).…”

Section: Results Of Phase Imentioning

confidence: 99%

“…The 20 MFS patients with no detected (likely) pathogenic FBN1 mutation had an average age of 27 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) years and a median systemic score of 7.5 (ranging from 6 to 9). Therefore, in terms of the systemic score, there was no significant difference between people with or without identified mutations (p = 0.100), but people without identified mutations were significantly younger (p = 0.011).…”

Section: Results Of Phase Imentioning

confidence: 99%

“…These involved the following 9 genes: ACTA2, COL3A1, FBN1, KCNN1, MYH11, SMAD3, TGFB2, TGFBR1 and TGFBR2. The mutations of these genes can lead to heritable aortopathies, including MFS, LDS, vascular Ehlers-Danlos syndrome (vEDS) and familial thoracic aortic aneurysm and dissection (FTAAD) [32]. With the multi-gene panel method, we examined the samples of a total number of 96 patients.…”

Section: Multi-gene Panel Analysismentioning

confidence: 99%

See 2 more Smart Citations

Optimising the mutation screening strategy in Marfan syndrome and identifying genotypes with more severe aortic involvement

Stengl

Bors

Ágg

et al. 2020

Orphanet J Rare Dis

View full text Add to dashboard Cite

Background Marfan syndrome (MFS) is a systemic connective tissue disorder with life-threatening manifestations affecting the ascending aorta. MFS is caused by dominant negative (DN) and haploinsufficient (HI) mutations of the FBN1 gene. Our aim was to identify mutations of MFS patients with high detection rate and to investigate the use of a gene panel for patients with Marfanoid habitus. We also aimed to examine correlations between genotype and cardiovascular manifestations to predict “malignant” mutations. Methods 136 individuals were enrolled. In the first phase, next-generation sequencing (NGS) and Sanger sequencing were performed for 57 patients to screen the FBN1 gene, followed by multiplex ligation-dependent probe amplification (MLPA) in negative cases. For repeated negative results, NGS gene panel involving 9 genes was used. In the second phase, 79 patients were tested primarily with the same gene panel, negative samples were tested by MLPA. Results 84 pathogenic mutations were detected, out of which 78 affected FBN1, 6 non-FBN1 mutations (2 TGFB2, 1 TGFBR2, 2 TGFBR1, 1 SMAD3) are associated with Loeys-Dietz syndrome (LDS). LDS patients had lower systemic score and they were younger, but their aortic involvement did not differ. MLPA detected 4 multi-exon deletions of FBN1 gene, which could not be identified by our first-step screening method. Aortic involvement (aortic dissection and/or dilation) did not differ significantly among HI and DN mutations (p = 0.061). Combined group of HI and DN mutations eliminating a disulphide-bonding cysteine (DN Cys) had significantly higher aortic involvement rate than DN mutations not eliminating a disulphide-bonding cysteine (DN non-Cys) (p < 0.001). Patients with DN Cys required significantly more aortic surgeries than HI and DN non-Cys mutations (p = 0.042 and p = 0.015, respectively). Conclusions Due to the relevant number of mutations affecting genes other than FBN1, preferred approach for testing individuals with Marfanoid habitus is using a gene panel rather than single-gene analysis, followed by MLPA for negative samples. DN Cys and HI mutations should be considered as risk factors for aortic involvement. Genetic testing for patients with Marfanoid features and a systemic score under 7 is recommended, as LDS patients may have lower scores, but they may have severe cardiovascular manifestations.

show abstract

Section: Results Of Phase Imentioning

confidence: 99%

Section: Results Of Phase Imentioning

confidence: 99%

Section: Multi-gene Panel Analysismentioning

confidence: 99%

See 1 more Smart Citation

Optimising the mutation screening strategy in Marfan syndrome and identifying genotypes with more severe aortic involvement

Stengl

Bors

Ágg

et al. 2020

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…2,4 Life-threatening complications can require emergency intervention without prior warning, with increased risk of subsequent morbidity and potential loss of physical function. 1,5,6 The autosomal-dominant mode of inheritance can cause anxiety about pregnancy for the patient's own health and the health of their children. Being diagnosed with an HTAAD diagnosis and getting acquainted with the consequences for themselves and their children may be experienced as a shock and life crisis.…”

Section: Hereditary Thoracic Aortic Aneurysm and Dissectionmentioning

confidence: 99%

“…The most serious complications in HTAAD diagnoses are related to the cardiovascular system, with risk of aneurysm and dissection of the aorta and other large arteries . Life‐threatening complications can require emergency intervention without prior warning, with increased risk of subsequent morbidity and potential loss of physical function . The autosomal‐dominant mode of inheritance can cause anxiety about pregnancy for the patient's own health and the health of their children.…”

Section: Introductionmentioning

confidence: 99%

Systematic review of quality of life in persons with hereditary thoracic aortic aneurysm and dissection diagnoses

et al. 2019

View full text Add to dashboard Cite

The purpose of this study was to explore the literature on quality of life (QoL) in patients with hereditary thoracic aortic aneurysm and dissection (HTAAD); including Marfan syndrome (MFS), Loeys‐Dietz syndrome (LDS), vascular Ehlers‐Danlos syndrome (vEDS) and other HTAAD diagnoses, critically appraising and synthesizing the relevant literature. A systematic review was performed by searching the published literature using available medical, physical, psychological, social databases and other sources. Studies addressing QoL in persons with an HTAAD diagnosis, published in peer‐reviewed journals were assessed. Of 227 search results, 20 articles satisfied the eligibility criteria. No studies of QoL in LDS, vEDS, or other HTAAD were found, only on MFS. Most studies had been published in the last 3 years. All were cross‐sectional quantitative studies besides one pilot intervention study. Most studies were of small sample size, had low response rate or participants without verified diagnosis. Despite these limitations, most studies indicate that having an HTAAD diagnosis as MFS may negatively impact QoL, but few studies found any associations between the biomedical symptoms and decreased QoL. More research is needed on QoL in samples with verified HTAAD diagnosis to develop evidence‐based knowledge and appropriate guidelines for these diagnoses.

show abstract

Whole‐exome sequencing: Clinical characterization of pediatric and adult Italian patients affected by different forms of hereditary cardiovascular diseases

Lenarduzzi

Spedicati

Alessandrini

et al. 2023

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background Hereditary cardiovascular diseases comprise several different entities. In this study, we focused on cardiomyopathies (i.e., hypertrophic, dilated, arrhythmogenic, and left ventricular non‐compaction), channelopathies (i.e., Brugada syndrome and long QT syndrome), and aortopathies and pulmonary arterial hypertension (i.e., thoracic/abdominal aortic aneurysm and pulmonary arterial hypertension), and genetically characterized 200 Italian patients affected by these diseases. Methods We employed whole‐exome sequencing (WES), focused on four in silico gene panels, and the MLPA method for hypertrophic and arrhythmogenic right ventricular cardiomyopathy cases. Results Cardiomyopathies affected 87.5% of analyzed patients, channelopathies 7%, and aortopathies and pulmonary arterial hypertension 5.5%. The molecular diagnosis was confirmed for 21.5% of cases with a higher detection rate in familial forms (34%) than sporadic ones (14%). We highlighted the importance of family segregation to better understand the pathogenic role of the identified variants and their involvement in the clinical phenotype. Negative results could be ascribed to the high genetic and clinical heterogeneity of hereditary cardiovascular diseases; clinical follow‐up and revaluation of WES data will be essential. Conclusion This study highlights the importance of a multi‐step approach (WES and MLPA) to characterize hereditary cardiovascular diseases, provides crucial information for clinical management and recurrence risk estimation, and lays the foundation for future personalized therapies.

show abstract

The Genetics of Aortopathies in Clinical Cardiology

Cited by 38 publications

References 67 publications

Optimising the mutation screening strategy in Marfan syndrome and identifying genotypes with more severe aortic involvement

Optimising the mutation screening strategy in Marfan syndrome and identifying genotypes with more severe aortic involvement

Systematic review of quality of life in persons with hereditary thoracic aortic aneurysm and dissection diagnoses

Whole‐exome sequencing: Clinical characterization of pediatric and adult Italian patients affected by different forms of hereditary cardiovascular diseases

Contact Info

Product

Resources

About