Erdmann, Jeanette and Daehmlow, S. and Wischke, S. and Senyuva, M. and Werner, U. and Raible, J. and Tanis, N. and Dyachenko, S. and Hummel, M. and Hetzer, R. and Regitz-Zagrosek, V. (2003) Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy. CLINICAL GENETICS, 64 (4). pp. 339-349. ISSN 0009-9163
Full text not available from this repository.Abstract
Defects in nine sarcomeric protein genes are known to cause hypertrophic cardiomyopathy (HCM). Mutation types and frequencies in large cohorts of consecutive and unrelated patients have not yet been determined. We, therefore, screened HCM patients for mutations in six sarcomeric genes: myosin-binding protein C3 (MYBPC3), MYH7, cardiac troponin T (TNNT2), alpha-tropomyosin (TPM1), cardiac troponin I (TNNI3), and cardiac troponin C (TNNC1). HCM was diagnosed in 108 consecutive patients by echocardiography (septum > 15 mm, septal/posterior wall > 1.3 mm), angiography, or based on a state after myectomy. Single-strand conformation polymorphism analysis was used for mutation screening, followed by DNA-sequencing. A total of 34 different mutations were identified in 108 patients: 18 mutations in MYBPC3 in 20 patients [intervening sequence (intron) 7 + 1G > A and Q1233X were found twice], 13 missense mutations in MYH7 in 14 patients (R807H was found twice), and one amino acid change in TPM1, TNNT2, and TNNI3, respectively. No disease-causing mutation was found in TNNC1. Cosegregation with the HCM phenotype could be demonstrated for 13 mutations (eight mutations in MYBPC3 and five mutations in MYH7). Twenty-eight of the 37 mutation carriers (76%) reported a positive family history with at least one affected first-grade relative; only eight mutations occurred sporadically (22%). MYBPC3 was the gene that most frequently caused HCM in our population. Systematic mutation screening in large samples of HCM patients leads to a genetic diagnosis in about 30% of unrelated index patients and in about 57% of patients with a positive family history.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BINDING PROTEIN-C; HEAVY-CHAIN GENE; BETA-CARDIAC MYOSIN; ALPHA-TROPOMYOSIN; DISEASE GENE; IDENTIFICATION; POPULATION; SARCOMERE; SITE; genetic diagnosis; hypertrophic cardiomyopathy; mutation; sarcomeric genes; SSCP |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Aug 2021 07:45 |
| Last Modified: | 30 Aug 2021 07:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38539 |
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