Characterization of a novel S13F desmin mutation associated with desmin myopathy and heart block in a Chinese family

Pica, Emmanuel C.; Kathirvel, Paramasivam; Pramono, Zacharias Aloysius Dwi; Lai, Poh-San; Yee, Woon Chee

doi:10.1016/j.nmd.2007.09.011

Cited by 26 publications

(24 citation statements)

References 12 publications

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“…We have summarised our Dutch data together with the data published on four Singapore-Chinese p.S13F carriers [12] (Table 2). Many patients show a severe cardiac phenotype, including sudden cardiac death or progressive heart failure: 14 of 39 known and obligate carriers died, underwent transplantation, or experienced appropriate implantable cardioverter defibrillator (ICD) interventions at a mean age of 48.4 years (range 27–63 years).…”

Section: Resultsmentioning

confidence: 99%

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Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D

Spaendonck‐Zwarts

Kooi²,

Berg

et al. 2012

Neth Heart J

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BackgroundDesmin-related myopathy (DRM) is an autosomally inherited skeletal and cardiac myopathy, mainly caused by dominant mutations in the desmin gene (DES). We describe new families carrying the p.S13F or p.N342D DES mutations, the cardiac phenotype of all carriers, and the founder effects.MethodsWe collected the clinical details of all carriers of p.S13F or p.N342D. The founder effects were studied using genealogy and haplotype analysis.ResultsWe identified three new index patients carrying the p.S13F mutation and two new families carrying the p.N342D mutation. In total, we summarised the clinical details of 39 p.S13F carriers (eight index patients) and of 21 p.N342D carriers (three index patients). The cardiac phenotype of p.S13F carriers is fully penetrant and severe, characterised by cardiac conduction disease and cardiomyopathy, often with right ventricular involvement. Although muscle weakness is a prominent and presenting symptom in p.N342D carriers, their cardiac phenotype is similar to that of p.S13F carriers. The founder effects of p.S13F and p.N342D were demonstrated by genealogy and haplotype analysis.ConclusionDRM may occur as an apparently isolated cardiological disorder. The cardiac phenotypes of the DES founder mutations p.S13F and p.N342D are characterised by cardiac conduction disease and cardiomyopathy, often with right ventricular involvement.Electronic supplementary materialThe online version of this article (doi:10.1007/s12471-011-0233-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

“…Haplotype analysis demonstrated an identical haplotype for six microsatellite markers in carriers of the available (7/8) Dutch families (see online supplement). Analysis revealed a different haplotype in a Singapore-Chinese p.S13F carrier (individual Pica II-3) [12] (see online supplement). …”

Section: Resultsmentioning

confidence: 99%

Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D

Spaendonck‐Zwarts

Kooi²,

Berg

et al. 2012

Neth Heart J

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“…These include S2I [13], S7F [18], S12F [20], S13F [21, 22], and S46F/Y [13]; 4) Serine residues 6, 7 and 8 are reversibly phosphorylated and their mutation dominantly effects myofibrillogenesis in cell culture models [23]. 5) WES of this patient did not identify mutations in any other genes associated with myofibrillar myopathies or vacuolar myopathies including LAMP2, VMA21 or CLN3 .…”

Section: Discussionmentioning

confidence: 99%

Autophagic vacuolar pathology in desminopathies

Weihl

Iyadurai

Baloh

et al. 2015

Neuromuscular Disorders

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Autophagic vacuolar myopathies (AVMs) are an emerging group of muscle diseases with common pathologic features. These include autophagic vacuoles containing both lysosomal and autophagosomal proteins sometimes lined with sarcolemmal proteins such as dystrophin. These features have been most clearly described in patients with Danon’s disease due to LAMP2 deficiency and X-linked myopathy with excessive autophagy (XMEA) due to mutations in VMA21. Disruptions of these proteins lead to lysosomal dysfunction and subsequent autophagic vacuolar pathology. We performed whole exome sequencing on two families with autosomal dominantly inherited myopathies with autophagic vacuolar pathology and surprisingly identified a p.R454W tail domain mutation and a novel p.S6W head domain mutation in desmin, DES. In addition, re-evaluation of muscle tissue from another family with a novel p.I402N missense DES mutation also identified autophagic vacuoles. We suggest that autophagic vacuoles may be an underappreciated pathology present in desminopathy patient muscle. Moreover, autophagic vacuolar pathology can be due to genetic etiologies unrelated to primary defects in the lysosomes or autophagic machinery. Specifically, cytoskeletal derangement and the accumulation of aggregated proteins such as desmin may activate the autophagic system leading to the pathologic features of an AVM.

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“…It was first described by Bergman et al 3 in 2007 in 2 Dutch families presenting a phenotype varying from isolated dilated cardiomyopathy to a generalized skeletal myopathy with mild respiratory problems. Pica et al 2 in 2008 published the mutation in a Chinese patient presenting a complete heart block associated with mild proximal and distal limb weakness. In 2009, van Tintelen et al 1 gave a precise description of the clinical presentation of 27 patients from 5 families.…”

Section: Discussionmentioning

confidence: 99%

“…The variant fulfilled all the criteria for a disease-causing mutation. Additionally, this mutation was already published as pathogenic1, 2, 3 and is located in the head domain of the protein. No mutation was identified in the lamin A/C gene.…”

Section: Case Reportmentioning

confidence: 99%

Recurrent suspected myocarditis combined with infrahisian conduction disturbances revealing a desminopathy

Boulé

Richard

Groote

et al. 2015

HeartRhythm Case Reports

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Characterization of a novel S13F desmin mutation associated with desmin myopathy and heart block in a Chinese family

Cited by 26 publications

References 12 publications

Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D

Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D

Autophagic vacuolar pathology in desminopathies

Recurrent suspected myocarditis combined with infrahisian conduction disturbances revealing a desminopathy

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