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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Diagnostic yield, interpretation, and clinical utility of mutation screening of sarcomere encoding genes in Danish hypertrophic cardiomyopathy patients and relatives
Human Mutation, Volume 30, No. 3, Year 2009
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Description
The American Heart Association (AHA) recommends family screening for hypertrophic cardiomyopathy (HCM). We assessed the outcome of family screening combining clinical evaluation and screening for sarcomere gene mutations in a cohort of 90 Danish HCM patients and their close relatives, in all 451 persons. Index patients were screened for mutations in all coding regions of 10 sarcomere genes (MYH7, MYL3, MYBPC3, TNNI3, TNNT2, TPM1, ACTC, CSRP3, TCAP, and TNNC1) and five exons of TTN. Relatives were screened for presence of minor or major diagnostic criteria for HCM and tracking of DNA variants was performed. In total, 297 adult relatives (418 years) (51.2%) fulfilled one or more criteria for HCM. A total of 38 HCM-causing mutations were detected in 32 index patients. Six patients carried two disease-associated mutations. Twenty-two mutations have only been identified in the present cohort. The genetic diagnostic yield was almost twice as high in familial HCM (53%) vs. HCM of sporadic or unclear inheritance (19%). The yield was highest in families with an additional history of HCM-related clinical events. In relatives, 29.9% of mutation carriers did not fulfil any clinical diagnostic criterion, and in 37.5% of relatives without a mutation, one or more criteria was fulfilled. A total of 60% of family members had no mutation and could be reassured and further follow-up ceased. Genetic diagnosis may be established in approximately 40% of families with the highest yield in familial HCM with clinical events. Mutation-screening was superior to clinical investigation in identification of individuals not at increased risk, where follow-up is redundant, but should be offered in all families with relatives at risk for developing HCM. © 2008 Wiley-Liss, Inc.
Authors & Co-Authors
Skyt Andersen, Paal Skytt
Denmark, Copenhagen
Statens Serum Institut
Havndrup, Ole
Denmark, Copenhagen
Rigshospitalet
Hougs, Lotte
Denmark, Copenhagen
Statens Serum Institut
Sørensen, Karina M.
Denmark, Copenhagen
Statens Serum Institut
Kvistholm Jensen, Morten Kvistholm
Denmark, Copenhagen
Rigshospitalet
Larsen, Lars A.
Denmark, Copenhagen
Københavns Universitet
Hedley, P. L.
Denmark, Copenhagen
Statens Serum Institut
South Africa, Stellenbosch
Stellenbosch University
Thomsen, Alex Rojas Bie
Denmark, Copenhagen
Statens Serum Institut
Moolman-Smook, Johanna Catharina
South Africa, Stellenbosch
Stellenbosch University
Christiansen, Michael
Denmark, Copenhagen
Statens Serum Institut
Bundgaard, Henning
Denmark, Copenhagen
Rigshospitalet
Statistics
Citations: 129
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1002/humu.20862
ISSN:
10597794
Research Areas
Cancer
Genetics And Genomics
Study Design
Cohort Study