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Molecular analysis of sarcomeric and non-sarcomeric genes in patients with hypertrophic cardiomyopathy.
- Source :
-
Gene [Gene] 2016 Feb 15; Vol. 577 (2), pp. 227-35. Date of Electronic Publication: 2015 Dec 02. - Publication Year :
- 2016
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Abstract
- Background: Hypertrophic cardiomyopathy (HCM) is a common genetic heart disorder characterized by unexplained left ventricle hypertrophy associated with non-dilated ventricular chambers. Several genes encoding heart sarcomeric proteins have been associated to HCM, but a small proportion of HCM patients harbor alterations in other non-sarcomeric loci. The variable expression of HCM seems influenced by genetic modifier factors and new sequencing technologies are redefining the understanding of genotype-phenotype relationships, even if the interpretations of the numerous identified variants pose several challenges.<br />Methods and Results: We investigated 62 sarcomeric and non-sarcomeric genes in 41 HCM cases and in 3 HCM-related disorders patients. We employed an integrated approach that combines multiple tools for the prediction, annotation and visualization of functional variants. Genotype-phenotype correlations were carried out for inspecting the involvement of each gene in age onset and clinical variability of HCM. The 80% of the non-syndromic patients showed at least one rare non-synonymous variant (nsSNV) and among them, 58% carried alterations in sarcomeric loci, 14% in desmosomal and 7% in other non-sarcomeric ones without any sarcomere change. Statistical analyses revealed an inverse correlation between the number of nsSNVs and age at onset, and a relationship between the clinical variability and number and type of variants.<br />Conclusions: Our results extend the mutational spectrum of HCM and contribute in defining the molecular pathogenesis and inheritance pattern(s) of this condition. Besides, we delineate a specific procedure for the identification of the most likely pathogenetic variants for a next generation sequencing approach embodied in a clinical context.<br /> (Copyright © 2015 Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1879-0038
- Volume :
- 577
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Gene
- Publication Type :
- Academic Journal
- Accession number :
- 26656175
- Full Text :
- https://doi.org/10.1016/j.gene.2015.11.048