A molecular screening strategy based on β-myosin heavy chain, cardiac myosin binding protein C and troponin T genes in Italian patients with hypertrophic cardiomyopathy

Girolami, Francesca; Olivotto, Iacopo; Passerini, Ilaria; Zachara, Elisabetta; Nistri, Stefano; Re, Federica; Fantini, Silvia; Baldini, Katia; Torricelli, Francesca; Cecchi, Fabiola

doi:10.2459/01.jcm.0000237908.26377.d6

Cited by 69 publications

(64 citation statements)

References 35 publications

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“…These variants have previously been associated with cardiomyopathy [18][19][20] a clinical feature not detected in our two patients. A similar scenario occurs for the nonsense c.4363G > T/p.Glu1455*, already reported elsewhere [21].…”

Section: Previously Described Mutationsmentioning

confidence: 77%

MYH7-related myopathies: Clinical, histopathological and imaging findings in a cohort of Italian patients

Savarese

Astrea

Cassandrini

et al. 2015

Neuromuscular Disorders

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Background: Myosin heavy chain 7 (MYH7)-related myopathies are emerging as an important group of muscle diseases of childhood and adulthood, with variable clinical and histopathological expression depending on the type and location of the mutation. Mutations in the head and neck domains are a well-established cause of hypertrophic cardiomyopathy whereas mutation in the distal regions have been associated with a range of skeletal myopathies with or without cardiac involvement, including Laing distal myopathy and Myosin storage myopathy. Recently the spectrum of clinical phenotypes associated with mutations in MYH7 has increased, blurring this scheme and adding further phenotypes to the list. A broader disease spectrum could lead to misdiagnosis of different congenital myopathies, neurogenic atrophy and other neuromuscular conditions. Results: As a result of a multicenter Italian study we collected clinical, histopathological and imaging data from a population of 21 cases from 15 families, carrying reported or novel mutations in MYH7. Patients displayed a variable phenotype including atypical pictures, as dropped head and bent spine, which cannot be classified in previously described groups. Half of the patients showed congenital or early infantile weakness with predominant distal weakness. Conversely, patients with later onset present prevalent proximal weakness. Seven patients were also affected by cardiomyopathy mostly in the form of non-compacted left ventricle. Muscle biopsy was consistent with minicores myopathy in numerous cases. Muscle MRI was meaningful in delineating a shared pattern of selective involvement of tibialis anterior muscles, with relative sparing of quadriceps. Conclusion: This work adds to the genotype-phenotype correlation of MYH7-relatedmyopathies confirming the complexity of the disorder.

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Section: Previously Described Mutationsmentioning

confidence: 77%

MYH7-related myopathies: Clinical, histopathological and imaging findings in a cohort of Italian patients

Savarese

Astrea

Cassandrini

et al. 2015

Neuromuscular Disorders

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“…In more than half of the HCM patients the disease-causing mutation is currently detected. 8,9 In the Netherlands 90% of mutations are identified in the myosin-binding protein C (MYBPC3) gene, in about 35 -40% of families this concerns the c.2373_2374insG mutation, one of the three Dutch founder mutations. 10 Mean age of diagnosis of HCM patients reported in literature is in their late thirties.…”

Section: Introductionmentioning

confidence: 99%

Uptake of genetic counselling and predictive DNA testing in hypertrophic cardiomyopathy

et al. 2008

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Hypertrophic cardiomyopathy is a common autosomal dominant disease, associated with heart failure and arrhythmias predisposing to sudden cardiac death. After the detection of the causal mutation in the proband predictive DNA testing of relatives is possible (cascade screening). Prevention of sudden cardiac death in patients with a high risk by means of an implantable cardioverter defibrillator is effective. In 97 hypertrophic cardiomyopathy families with a sarcomere gene mutation we retrospectively determined uptake of genetic counselling and predictive DNA testing in relatives within 1 year after the detection of the causal mutation in the proband. Uptake of genetic counselling was 39% and did not differ significantly by proband's or relative's gender, nor by young age of the relative (o18 years) or a family history positive for sudden cardiac death. In second-degree relatives, eligible for predictive DNA testing when the firstdegree relative had died, uptake was 27.5% (P ¼ 0.047). Uptake of predictive genetic testing was 39%; conditional uptake of predictive genetic testing was 99%. Uptake of genetic counselling in hypertrophic cardiomyopathy is comparable to uptake in oncogenetics. Conditional uptake of predictive DNA testing, however, is much higher. Because sudden cardiac death can be prevented uptake of genetic counselling in hypertrophic cardiomyopathy should be as high as possible. To achieve this research into the determinants of uptake is needed.

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“…9 In conjunction with the genetic heterogeneity of HCM, phenotypic expression of HCM also exhibits a high level of variability. 10 This variability can be attributable to several factors such as hypertension, 11 vigorous athletic competi tion, 12 alcohol consumption, 13 the presence of double or triple sarcomeric mutations together, 14 mutations in mito chondrial DNA such as in the Kearns-Sayre syndrome, 15 triplet repeats mutations, as happens in the myotonic mus cular dystrophy and Friedreich's ataxia, 16 or mutations in nonsarcomeric proteins.…”

Section: Introductionmentioning

confidence: 99%

Impact of polymorphisms in the renin–angiotensin–aldosterone system on hypertrophic cardiomyopathy

Orenes‐Piñero

Hernández-Romero

Jover

et al. 2011

J Renin Angiotensin Aldosterone Syst

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Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous autosomal dominant heart disease characterised by left ventricular hypertrophy in the absence of another cardiac or systemic disease that is capable of producing significant wall thickening. Microscopically it is characterised by cardiomyocyte hypertrophy, myofibrillar disarray and fibrosis. The phenotypic expression of HCM is multifactorial, with the majority of cases occurring secondary to mutations in genes encoding the sarcomere proteins. In conjunction with the genetic heterogeneity of HCM, phenotypic expression also exhibits a high level of variability even within families with the same aetiological mutation, and may be influenced by additional genetic factors. Polymorphisms of the renin-angiotensin-aldosterone system (RAAS) represent an attractive hypothesis as potential disease modifiers, as these genetic variants alter the 'activation status' of the RAAS, which leads to more left ventricular hypertrophy through different pathways. The main objective of this review is to provide an overview of the role of different polymorphisms identified in the RAAS, in patients with HCM.

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A molecular screening strategy based on β-myosin heavy chain, cardiac myosin binding protein C and troponin T genes in Italian patients with hypertrophic cardiomyopathy

Cited by 69 publications

References 35 publications

MYH7-related myopathies: Clinical, histopathological and imaging findings in a cohort of Italian patients

MYH7-related myopathies: Clinical, histopathological and imaging findings in a cohort of Italian patients

Uptake of genetic counselling and predictive DNA testing in hypertrophic cardiomyopathy

Impact of polymorphisms in the renin–angiotensin–aldosterone system on hypertrophic cardiomyopathy

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