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. 2023 May;11(5):e2143.
doi: 10.1002/mgg3.2143. Epub 2023 Feb 14.

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

Stefania Lenarduzzi  1 , Beatrice Spedicati  2 , Beatrice Alessandrini  2 , Paola Tesolin  2 , Alessia Paldino  3 , Marta Gigli  3 , Gianfranco Sinagra  2   3 , Paolo Gasparini  1   2 , Matteo Dal Ferro  3 , Giorgia Girotto  1   2
Affiliations

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

Stefania Lenarduzzi et al. Mol Genet Genomic Med. 2023 May.

Abstract

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.

Keywords: MLPA; hereditary cardiovascular diseases; whole-exome sequencing.

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Conflict of interest statement

The authors report no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Among the 200 patients, 87.5% were affected by cardiomyopathies, 7% suffer from Channelopathies, and 5.5% have aortopathies and pulmonary arterial hypertension as shown on the left pie chart. On the right, 27% of patients with hypertrophic cardiomyopathy, 55% dilated cardiomyopathy, 17% arrhythmogenic right ventricular cardiomyopathy, 1% left ventricular non‐compaction are shown. ARVC, Arrhythmogenic Right Ventricular Cardiomyopathy; CMs, Cardiomyopathies; DCM, Dilated Cardiomyopathy; HCM, Hypertrophic Cardiomyopathy; LVNC, Left Ventricular Non‐Compaction
FIGURE 2
FIGURE 2
Multiplex ligation‐dependent probe amplification results for CM596, CM745, and CM752. The analysis revealed the presence of three large deletions within the PKP2 gene (NM_004572.3) responsible for arrhythmogenic right ventricular cardiomyopathy. ARVC, Arrhythmogenic Right Ventricular Cardiomyopathy; MLPA, Multiplex Ligation‐dependent Probe Amplification
See this image and copyright information in PMC

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