Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2042-2048 |
| Number of pages | 7 |
| Journal | Journal of the American College of Cardiology |
| Volume | 39 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 19 2002 |
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Prevalence and age-dependence of malignant mutations in the beta-myosin heavy chain and troponin T genes in hypertrophic cardiomyopathy : A comprehensive outpatient perspective. / Ackerman, Michael John; VanDriest, Sara L.; Ommen, Steve R.; Will, Melissa L.; Nishimura, Rick A.; Tajik, A. Jamil; Gersh, Bernard J.
In: Journal of the American College of Cardiology, Vol. 39, No. 12, 19.06.2002, p. 2042-2048.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prevalence and age-dependence of malignant mutations in the beta-myosin heavy chain and troponin T genes in hypertrophic cardiomyopathy
T2 - A comprehensive outpatient perspective
AU - Ackerman, Michael John
AU - VanDriest, Sara L.
AU - Ommen, Steve R.
AU - Will, Melissa L.
AU - Nishimura, Rick A.
AU - Tajik, A. Jamil
AU - Gersh, Bernard J.
PY - 2002/6/19
Y1 - 2002/6/19
N2 - 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.
AB - 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.
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U2 - 10.1016/S0735-1097(02)01900-9
DO - 10.1016/S0735-1097(02)01900-9
M3 - Article
C2 - 12084606
AN - SCOPUS:0037134832
VL - 39
SP - 2042
EP - 2048
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
SN - 0735-1097
IS - 12
ER -