Molecular basis of facioscapulohumeral muscular dystrophy

Tupler, Rossella; Gabellini, Davide

doi:10.1007/s00018-003-3285-3

Cited by 55 publications

(46 citation statements)

References 60 publications

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“…Since the main locus of this hereditary arrhythmia maps on chromosome 4q25-7, in close proximity to the FSHD locus on 4q35 [22], the authors speculated on a relationship between the 2 diseases [14]. Notably this assumption would concur with the recent pathogenetic hypothesis [6, 7] that relates clinical FSHD manifestations to a position effect of 4q35 deletion on the proximal transcriptional genes.…”

Section: Discussionsupporting

confidence: 55%

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Facioscapulohumeral Muscular Dystrophy and Occurrence of Heart Arrhythmia

Trevisan¹,

Pastorello²,

Armani³

et al. 2006

Eur Neurol

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Background: Subjects with facioscapulohumeral muscular dystrophy (FSHD) do not generally suffer from significant cardiac symptoms. Although with heterogeneous results, studies reported to date indicate that heart alterations unrelated to cardiomyopathy are possible in FSHD. Patients and Methods: We describe the findings of a multicenter investigation aimed at detecting cardiac abnormalities in 83 FSHD patients, 44 males and 39 females with a mean age of 47 years. All patients underwent clinical heart examination, 12-lead electrocardiography and 24-hour Holter monitoring; echocardiography was also performed on most patients. Results: Among the 83 patients, 62 with no cardiovascular risk factors were identified. Ten of them manifested clinical or subclinical cardiac involvement: 5 reported symptoms represented mostly by frequent palpitations secondary to supraventricular arrhythmia and another 5 exhibited electrocardiographic signs of short runs of supraventricular paroxysmal tachycardia. In the absence of cardiovascular risk factors, we found symptoms or signs of heart involvement of mainly arrhythmic origin in 10 of our 83 FSHD patients (12%). Conclusions: Considering our data and those available in the literature as a whole, arrhythmic alterations seem to be detected more frequently than expected in FSHD patients.

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Section: Discussionsupporting

confidence: 55%

“…Genetically, this autosomal dominant disease was mapped in the chromosome 4q35 region [3], where the deletion of a tandem repeat of 3.3 kb (D4Z4) was detected [4, 5]. This DNA sequence is nontranscriptional, but seems to have a peculiar position effect on proximal upstream transcriptional genes [6, 7]. …”

Section: Introductionmentioning

confidence: 99%

Facioscapulohumeral Muscular Dystrophy and Occurrence of Heart Arrhythmia

Trevisan¹,

Pastorello²,

Armani³

et al. 2006

Eur Neurol

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show abstract

“…Recent laboratory data, however, support the hypothesis that the DNA deletion causes the FSHD phenotype by altering normal gene function, which operates as a silencer on the expression of proximal transcriptional genes. Different-sized 4q35 DNA deletions could determine different extensions of the position effect on proximal genes, thus explaining the variable disease phenotype [Tupler and Gabellini, 2004;Tawil and Van der Maarel, 2006].…”

Section: Discussionmentioning

confidence: 99%

“…DNA was extracted from peripheral blood, digested with the restriction enzyme Eco RI, double digested with Eco RI/ Bln I and hybridized with radioactivelabeled probe p13E-11, after separation by pulsed-field gel electrophoresis. These molecular analyses were performed as reported elsewhere Tupler and Gabellini, 2004].…”

Section: Molecular Diagnosismentioning

confidence: 99%

Facioscapulohumeral Muscular Dystrophy: A Multicenter Study on Hearing Function

et al. 2007

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Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant progressive myopathy, characteristically associated with a 4q35 deletion. In the unusual infantile-onset form of this degenerative disease, sensorineural hearing loss is a frequent clinical manifestation, whereas in patients with typical late-onset FSHD, investigations regarding hearing impairment yielded controversial results. We describe the findings of a multicenter investigation on possible auditory impairment in a series of 73 FSHD patients with a genetically confirmed diagnosis. Among them, 49 cases with no risk factors for deafness, aside from the disease, were identified by a clinical questionnaire and otoscopic examination (mean age 37.8 years, 31 males and 18 females). These subjects were evaluated by pure-tone audiometry. None were aware of hearing loss, while 4 had raised unilateral or bilateral pure-tone audiometric thresholds at 4000 and 8000 Hz, when evaluated by standardized tables. However, the mean raw pure-tone audiometric threshold values for these 49 cases were not significantly different from those of 55 controls (mean age 37.1 years, 32 males and 23 females). Moreover, by statistical analysis, age of onset, degree of muscular weakness and 4q35 EcoRI fragment size made no significant difference to auditory thresholds in our FSHD patients. Overall, the results of our multicenter study suggest that hearing loss in typical FSHD is not more prevalent than in the normal population.

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“…Bickmore and van der Maarel, and Gabellini and colleagues, proposed that contraction of the repeats causes a less repressive chromatin state leading to increased transcription of 4q35-qter genes (Bickmore and van der Maarel 2003;Tupler and Gabellini 2004). However, the loss of repressive H3K9 and DNA methylation marks alone was shown to be insufficient for myopathic gene derepression and FSHD onset, and therefore they are likely to be downstream epigenetic mechanisms, locking in a repressive chromatin state (Cabianca et al 2012).…”

Section: Facioscapulohumeral Dystrophymentioning

confidence: 99%

Epigenetics and Human Disease

Zoghbi

Beaudet

2016

Cold Spring Harb Perspect Biol

212

130

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SUMMARYGenetic causes for human disorders are being discovered at an unprecedented pace. A growing subclass of disease-causing mutations involves changes in the epigenome or in the abundance and activity of proteins that regulate chromatin structure. This article focuses on research that has uncovered human diseases that stem from such epigenetic deregulation. Disease may be caused by direct changes in epigenetic marks, such as DNA methylation, commonly found to affect imprinted gene regulation. Also described are disease-causing genetic mutations in epigenetic modifiers that either affect chromatin in trans or have a cis effect in altering chromatin configuration.

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Molecular basis of facioscapulohumeral muscular dystrophy

Cited by 55 publications

References 60 publications

Facioscapulohumeral Muscular Dystrophy and Occurrence of Heart Arrhythmia

Facioscapulohumeral Muscular Dystrophy and Occurrence of Heart Arrhythmia

Facioscapulohumeral Muscular Dystrophy: A Multicenter Study on Hearing Function

Epigenetics and Human Disease

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