OBJECTIVES: The goal of this study was to determine the prevalence of "malignant" mutations in hypertrophic cardiomyopathy (HCM). BACKGROUND: Previous genotype-phenotype studies have implicated four mutations (R403Q, R453C, G716R and R719W) as highly malignant defects in the beta-myosin heavy chain (MYH7). In the cardiac troponin T gene (TNNT2), a specific mutation (R92W) has been associated with high risk of sudden death. Routine clinical screening for these malignant mutations has been suggested to identify high-risk individuals. METHODS: We screened 293 unrelated individuals with HCM seen at the Mayo Clinic in Rochester, Minnesota, between April 1997 and October 2000. Deoxyribonucleic acid (DNA) was obtained after informed consent; amplification of MYH7 exons 13 (R403Q), 14 (R453C) and 19 (G716R and R719W), and TNNT2 exon 9 (R92W) was performed by polymerase chain reaction. The mutations were detected using denaturing high-performance liquid chromatography and automated DNA sequencing. RESULTS: The mean age at diagnosis was 42 years with 53 patients diagnosed before age 25. The mean maximal left ventricular wall thickness was 21 mm. Nearly one-third of cases were familial and one-fourth had a family history of sudden cardiac death. Only 3 of the 293 patients possessed one of the five "malignant" mutations, and all 3 patients were <25 years of age at presentation (p < 0.006). CONCLUSIONS: This finding underscores the profound genetic heterogeneity in HCM. Only 1% of unrelated individuals seen at a tertiary referral center for HCM possessed one of the five "malignant" mutations that were examined. Routine clinical testing for these specific mutations is of low yield.
OBJECTIVES: The goal of this study was to determine the prevalence of "malignant" mutations in hypertrophic cardiomyopathy (HCM). BACKGROUND: Previous genotype-phenotype studies have implicated four mutations (R403Q, R453C, G716R and R719W) as highly malignant defects in the beta-myosin heavy chain (MYH7). In the cardiac troponin T gene (TNNT2), a specific mutation (R92W) has been associated with high risk of sudden death. Routine clinical screening for these malignant mutations has been suggested to identify high-risk individuals. METHODS: We screened 293 unrelated individuals with HCM seen at the Mayo Clinic in Rochester, Minnesota, between April 1997 and October 2000. Deoxyribonucleic acid (DNA) was obtained after informed consent; amplification of MYH7 exons 13 (R403Q), 14 (R453C) and 19 (G716R and R719W), and TNNT2 exon 9 (R92W) was performed by polymerase chain reaction. The mutations were detected using denaturing high-performance liquid chromatography and automated DNA sequencing. RESULTS: The mean age at diagnosis was 42 years with 53 patients diagnosed before age 25. The mean maximal left ventricular wall thickness was 21 mm. Nearly one-third of cases were familial and one-fourth had a family history of sudden cardiac death. Only 3 of the 293 patients possessed one of the five "malignant" mutations, and all 3 patients were <25 years of age at presentation (p < 0.006). CONCLUSIONS: This finding underscores the profound genetic heterogeneity in HCM. Only 1% of unrelated individuals seen at a tertiary referral center for HCM possessed one of the five "malignant" mutations that were examined. Routine clinical testing for these specific mutations is of low yield.
Authors: I Christiaans; E A Nannenberg; D Dooijes; R J E Jongbloed; M Michels; P G Postema; D Majoor-Krakauer; A van den Wijngaard; M M A M Mannens; J P van Tintelen; I M van Langen; A A M Wilde Journal: Neth Heart J Date: 2010-05 Impact factor: 2.380
Authors: Sinead L Murphy; Jason H Anderson; Jamie D Kapplinger; Teresa M Kruisselbrink; Bernard J Gersh; Steve R Ommen; Michael J Ackerman; J Martijn Bos Journal: J Cardiovasc Transl Res Date: 2016-02-25 Impact factor: 4.132