Exome Sequencing and Genome-Wide Linkage Analysis in 17 Families Illustrates the Complex Contribution of TTN Truncating Variants to Dilated Cardiomyopathy
نویسندگان
چکیده
Nadine Norton, PhD1, Duanxiang Li, MD, MS1, Evadnie Rampersaud, PhD2, Ana Morales, MS, CGC1, Eden R. Martin, PhD2, Stephan Zuchner, MD2, Shengru Guo, MS2, Michael Gonzalez, BSc2, Dale J. Hedges, PhD2, Peggy D. Robertson, PhD3, Niklas Krumm, BA3, Deborah A. Nickerson, PhD3, and Ray E. Hershberger, MD1 on behalf of the National Heart Lung and Blood Institute GO Exome Sequencing Project & the Exome Sequencing Project Family Studies Project Team 1Cardiovascular Division, Dept of Medicine, University of Miami Miller School of Medicine, Miami, FL 2Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 3Dept of Genome Sciences, University of Washington, Seattle, WA
منابع مشابه
Exome sequencing and genome-wide linkage analysis in 17 families illustrate the complex contribution of TTN truncating variants to dilated cardiomyopathy.
BACKGROUND- Familial dilated cardiomyopathy (DCM) is a genetically heterogeneous disease with >30 known genes. TTN truncating variants were recently implicated in a candidate gene study to cause 25% of familial and 18% of sporadic DCM cases. METHODS AND RESULTS- We used an unbiased genome-wide approach using both linkage analysis and variant filtering across the exome sequences of 48 individual...
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Mutations in the gene encoding the giant skeletal muscle protein titin are associated with a variety of muscle disorders, including recessive congenital myopathies ±cardiomyopathy, limb girdle muscular dystrophy (LGMD) and late onset dominant distal myopathy. Heterozygous truncating mutations have also been linked to dilated cardiomyopathy. The phenotypic spectrum of titinopathies is emerging a...
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RESULTS We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P = 1.3×10−7) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P = 0.81). Two thir...
متن کاملShared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.
Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of diff...
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TTN gene truncating variants are common in dilated cardiomyopathy (DCM), although data on their clinical significance is still limited. We sought to examine the frequency of truncating variants in TTN in patients with DCM, including familial DCM (FDCM), and to look for genotype-phenotype correlations. Clinical cardiovascular data, family histories and blood samples were collected from 72 DCM pr...
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