Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy

Millat, Gilles; Bouvagnet, Patrice; Chevalier, Philippe; Dauphin, Claire; Jouk, Pierre‐Simon; Costa, Antoine Da; Prieur, Fabienne; Bresson, J.; Faivre, Laurence; Eicher, Jean‐Christophe; Chassaing, Nicolas; Crehalet, Hervé; Porcher, Raphaël; Rodriguez-Lafrasse, Claire; Rousson, Robert

doi:10.1016/j.ejmg.2010.07.007

Cited by 139 publications

(110 citation statements)

References 21 publications

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“…Fifteen cohort studies 7,[15][16][17][18][19][20][21][22][23][24][25][26][27][28] provided data on the percentage of double mutations out of genotype-positive patients in HCM cohorts ( Table 2). A panel including 8 to 10 genes was used for testing 33% of the patients included in these studies, 5 to 7 genes in 44%, and 2 to 4 genes in 23%.…”

Section: Cohort Studiesmentioning

confidence: 99%

Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy

Fourey

Care

Siminovitch

et al. 2017

Circ Cardiovasc Genet

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Background-Available data suggests that double mutations in patients with hypertrophic cardiomyopathy are not rare and are associated with a more severe phenotype. Most of this data, however, is based on noncontemporary variant classification. Methods and Results-Clinical data of all hypertrophic cardiomyopathy patients with 2 rare genetic variants were retrospectively reviewed and compared with a group of patients with a single disease-causing variant. Furthermore, a literature search was performed for all studies with information on prevalence and outcome of patients with double mutations. Classification of genetic variants was reanalyzed according to current guidelines. In our cohort (n=1411), 9% of gene-positive patients had 2 rare variants in sarcomeric genes but only in 1 case (0.4%) were both variants classified as pathogenic. Patients with 2 rare variants had a trend toward younger age at presentation when compared with patients with a single mutation. All other clinical variables were similar. In data pooled from cohort studies in the literature, 8% of gene-positive patients were published to have double mutations. However, after reanalysis of reported variants, this prevalence diminished to 0.4%. All patients with 2 radical mutations in MYBPC3 in the literature had severe disease with death or heart transplant during the first year of life. Data on other specific genotype-phenotype correlations were scarce. Conclusions-Double mutations in patients with hypertrophic cardiomyopathy are much less common than previously estimated. With the exception of double radical MYBPC3 mutations, there is little data to guide clinical decision making in cases with double mutations. (Circ Cardiovasc

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Section: Cohort Studiesmentioning

confidence: 99%

Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy

Fourey

Care

Siminovitch

et al. 2017

Circ Cardiovasc Genet

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“…Table 1 shows the mutations of probands. [21][22][23][24][25][26][27][28][29] The clinical charac- teristics of affected family members at initial diagnosis are presented in Table 2. A comparison of the clinical characteristics between sarcomere mutation-positive and sarcomere mutation-negative probands was performed (Table 3).…”

Section: Resultsmentioning

confidence: 99%

“…The patient presented with congestive heart failure at age 63 ( Figure 2C and 2D). His 2 affected, asymptomatic children, a 32-year-old daughter (II-2) and a 34-year-old son (II-3), were 24 Niimura et al, 25 and Millat et al, 26 18 Arad et al, 27 and Monserrat et al 28 LVNC-111 SA c.478GϾA p.Glu101Lys 2 Klaassen et al, 18 Arad et al, 27 and Monserrat et al 28 …”

Section: Mutations In ␣-Tropomyosinmentioning

confidence: 99%

Sarcomere Gene Mutations in Isolated Left Ventricular Noncompaction Cardiomyopathy Do Not Predict Clinical Phenotype

Probst

Oechslin

Schuler

et al. 2011

Circ Cardiovasc Genet

178

110

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Background-Left ventricular noncompaction of the myocardium (LVNC) has been recognized as a cardiomyopathy with a genetic etiology. Mutations in genes encoding sarcomere proteins were shown to be associated with LVNC. We evaluated the potential clinical impact of genetic analysis of sarcomere genes in patients with LVNC. Methods and Results-We identified 5 mutations in cardiac myosin-binding protein C (MYBPC3) and 2 mutations in ␣-tropomyosin (TPM1) in a cohort of unrelated adult probands with isolated LVNC. The mutations in MYBPC3 and TPM1 and in 6 other previously reported sarcomere genes in this cohort resulted in a total of 18 (29%) heterozygous mutations in 63 probands. ␤-myosin heavy chain (MYH7) was the most prevalent disease gene and accounts for 13% of cases, followed by MYBPC3 (8%). Comparing sarcomere mutation-positive and mutation-negative LVNC probands showed no significant differences in terms of average age, myocardial function, and presence of heart failure or tachyarrhythmias at initial presentation or at follow-up. Familial disease was found in 16 probands of whom 8 were sarcomere mutation positive. Nonpenetrance was detected in 2 of 8 mutation-positive families with LVNC. Conclusions-Mutations

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“…[75][76][77] Multiple mutations are also not uncommon. 78 Whether genetic information improves risk stratification for SCD over and above phenotypic markers is not known.…”

Section: Severe Left Ventricular Hypertrophymentioning

confidence: 99%

Sudden Cardiac Death in Hypertrophic Cardiomyopathy

O’Mahony

Elliott

McKenna

2013

Circ: Arrhythmia and Electrophysiology

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SCD in HCM has been linked with physical exertion. 33 A vicious cycle of increasing myocardial ischemia, caused by diastolic dysfunction, LVOTO, systemic hypotension, and decreased stroke volume, has been suggested, but SCD can occur at rest or sleep, 33 when metabolic demands are low. The exact triggers of ventricular arrhythmias remain unclear. Risk Factors of SCD in HCMVarious phenotypic characteristics have been linked with SCD and are currently used to identify patients at risk. 34,35 These risk factors were first noted in small, comparative observational studies, and then re-examined in larger studies with multivariable survival analysis using the Cox proportional

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Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy

Cited by 139 publications

References 21 publications

Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy

Prevalence and Clinical Implication of Double Mutations in Hypertrophic Cardiomyopathy

Sarcomere Gene Mutations in Isolated Left Ventricular Noncompaction Cardiomyopathy Do Not Predict Clinical Phenotype

Sudden Cardiac Death in Hypertrophic Cardiomyopathy

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