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A. Van Den Wijngaard, P. Volders, J. P. Van Tintelen, J. D.H. Jongbloed, M. P. Van Den Berg, R. H. Lekanne Deprez, M. M.A.M. Mannens, N. Hofmann, M. Slegtenhorst, D. Dooijes, M. Michels, Y. Arens, R. Jongbloed, B. J.M. Smeets
Research output: Chapter in Book/Report/Conference proceeding › Chapter › Academic › peer-review
Background: About 2-7% of familial cardiomyopathy cases are caused by a mutation in the gene encoding cardiac troponin I (TNNI3). The related clinical phenotype is usually severe with early onset. Here we report on all currently known mutations in the Dutch population and compared these with those described in literature.
Methods: The TNNI3 gene was screened for mutations in all coding exons and flanking intronic sequences in a large cohort of cardiomyopathy patients. All Dutch index cases carrying a TNNI3 mutation that are described in this study underwent extensive cardiological evaluation and were listed by their postal codes.
Results: In 30 families, 14 different mutations were identified. Three TNNI3 mutations were found relatively frequently in both familial and non-familial cases of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM). Haplotype analysis showed that p.Arg145Trp and p.Ser166Phe are founder mutations in the Netherlands, while p.Glu209Ala is not. The majority of Dutch TNNI3 mutations were associated with a HCM phenotype. Mean age at diagnosis was 36.5 years. Mutations causing RCM occurred less frequently, but were identified in very young children with a poor prognosis.
Conclusion: In line with previously published data, we found TNNI3 mutations to be rare and associated with early onset and severe clinical presentation.
Original language | English |
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Title of host publication | Founder Mutations in Inherited Cardiac Diseases in the Netherlands |
Publisher | Bohn Stafleu Van Loghum bv |
Pages | 43-50 |
Number of pages | 8 |
ISBN (Electronic) | 9789036807050 |
ISBN (Print) | 9036807042, 9789036807043 |
DOIs | |
Publication status | Published - 1-Nov-2014 |
Research output: Contribution to journal › Article › Academic › peer-review