Key result
Whole-exome sequencing and MLPA confirmed a molecular diagnosis in 21.5% of patients with hereditary cardiovascular diseases, with a higher detection rate in familial versus sporadic forms.
Why the study?
Hereditary cardiovascular diseases comprise several different entities, warranting genetic characterization across cardiomyopathies, channelopathies, aortopathies, and pulmonary arterial hypertension.
Observational (n=200)
A multi-step genetic testing approach using whole-exome sequencing and MLPA yields a molecular diagnosis in approximately one-fifth of patients with hereditary cardiovascular diseases, with a significantly higher yield in familial cases.
Answers are grounded in this paper and cite their sources.
Supports targeted genetic testing in familial hereditary CVD; leaves open broader utility and prospective validation in sporadic cases.
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.
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Lenarduzzi et al. (2023) conducted an observational in Hereditary cardiovascular diseases (n=200). Whole-exome sequencing (WES) and MLPA was evaluated on Molecular diagnosis confirmation. Whole-exome sequencing and MLPA confirmed a molecular diagnosis in 21.5% of patients with hereditary cardiovascular diseases, with a higher detection rate in familial versus sporadic forms.
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