Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects

Arbustini, Eloisa; Pasotti, Michele; Pilotto, Andrea; Pellegrini, Carlo; Grasso, Maurizia; Previtali, Stefano C.; Repetto, Alessandra; Bellini, O; Azan, G.; Scaffino, Manuela; Campana, Carlo; Piccolo, G.; Viganò, Mario; Tavazzi, Luigi

doi:10.1016/j.ejheart.2005.11.003

Cited by 168 publications

(137 citation statements)

References 26 publications

Supporting

Mentioning

111

Contrasting

Unclassified

Order By: Relevance

“…Additional cardiopathological findings have been reported based on examination of cardiac biopsies or explanted hearts. 37,43,52,56 In all described cases, microscopic examination revealed protein aggregates in the center of cardiac muscle fibre, rather than subsarcolemmally, hypertrophy of cardiomyocytes, prominent nuclei and considerable interstitial fibrosis (Fig. 8).…”

Section: Cardiac and Smooth Muscle Pathologymentioning

confidence: 83%

“…The primary syndrome in seven patients from four families was RCM with atrio-ventricular block; 37 only two patients showed clinical evidence of skeletal myopathy. Desmin accumulation was demonstrated in the myocardial and skeletal muscle samples.…”

Section: Cardiomyopathymentioning

confidence: 97%

“…Desminopathy-associated atrioventricular conduction blocks may be associated with RCM, DCM and HCM. 37,46,55 Skeletal muscle weakness followed by cardiomyopathy was observed in 31 patients from 20 families ( Table 2). A p.Leu345Pro mutation within the 2B helix 6 was detected in a family that included 16 members suffering from gait disturbances caused by bilateral weakness in distal leg muscles that progressed to all limbs and bulbar, respiratory and facial muscles.…”

Section: Cardiomyopathymentioning

confidence: 99%

See 2 more Smart Citations

Intermediate Filament Diseases: Desminopathy

Goldfarb

Olivé

Vicart³

et al. 2008

Advances in Experimental Medicine and Biology

104

View full text Add to dashboard Cite

Desminopathy is one of the most common intermediate filament human disorders associated with mutations in closely interacting proteins, desmin and alphaB-crystallin. The inheritance pattern in familial desminopathy is characterized as autosomal dominant or autosomal recessive, but many cases have no family history. At least some and likely most sporadic desminopathy cases are associated with de novo DES mutations. The age of disease onset and rate of progression may vary depending on the type of inheritance and location of the causative mutation. Typically, the illness presents with lower and later upper limb muscle weakness slowly spreading to involve truncal, neckflexor, facial and bulbar muscles. Skeletal myopathy is often combined with cardiomyopathy manifested by conduction blocks, arrhythmias and chronic heart failure resulting in premature sudden death. Respiratory muscle weakness is a major complication in some patients. Sections of the affected skeletal and cardiac muscles show abnormal fibre areas containing chimeric aggregates consisting of desmin and other cytoskeletal proteins. Various DES gene mutations: point mutations, an insertion, small in-frame deletions and a larger exon-skipping deletion, have been identified in desminopathy patients. The majority of these mutations are located in conserved alpha-helical segments, but additional mutations have recently been identified in the tail domain. Filament and network assembly studies indicate that most but not all disease-causing mutations make desmin assembly-incompetent and able to disrupt a pre-existing filamentous network in dominant-negative fashion. AlphaBcrystallin serves as a chaperone for desmin preventing its aggregation under various forms of stress; mutant CRYAB causes cardiac and skeletal myopathies identical to those resulting from DES mutations.

show abstract

Section: Cardiac and Smooth Muscle Pathologymentioning

confidence: 83%

Section: Cardiomyopathymentioning

confidence: 97%

Section: Cardiomyopathymentioning

confidence: 99%

See 1 more Smart Citation

Intermediate Filament Diseases: Desminopathy

Goldfarb

Olivé

Vicart³

et al. 2008

Advances in Experimental Medicine and Biology

104

View full text Add to dashboard Cite

show abstract

“…Restrictive cardiomyopathy by deposition of desmin is usually associated with electrophysiological abnormalities of cardiac stimulus conduction, particularly different degrees of AVB [1][2][3] . Ventricular tachycardia may also occur in this disease.…”

Section: Discussionmentioning

confidence: 99%

“…Besides the restriction to diastolic ventricular filling, patients usually present clinical or subclinical skeletal myopathy and varying degrees of atrioventricular block (AVB) [1][2][3] . Although several cases of the disease have been previously reported, the morphological basis for the development of AVB has not been studied.…”

Section: Introductionmentioning

confidence: 99%

Patologia do bloqueio atrioventricular na cardiomiopatia por depósito de desmina

Benvenuti¹,

Aiello²,

Falcão³

et al. 2012

Arq. Bras. Cardiol.

View full text Add to dashboard Cite

KeywordsAtrioventricular block/pathology, restrictive cardiomyopathy, desmin, heart conduction system. Generally, restrictive cardiomyopathy due to desmin deposition is characterized by restriction to ventricular diastolic filling and different degrees of atrioventricular block (AVB). In this report, we describe the pathological changes of the cardiac conduction system related to AVB. The sinus node, the compact node, and the penetrating bundle (bundle of His) had no abnormalities, however, there was extensive fibrosis of the terminal portions of the branching bundle and the beginning of the left and right bundles at the top of the ventricular septum. The pathogenesis of this fibrous replacement is probably the same that leads to extensive fibrosis of the working ventricular myocardium, and remains to be elucidated.

show abstract

Evidence for troponin C (TNNC1) as a gene for autosomal recessive restrictive cardiomyopathy with fatal outcome in infancy

Płoski

Rydzanicz

Książczyk

et al. 2016

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Restrictive cardiomyopathy is a rare form of pediatric cardiac disease, for which the known genes include MYH7, TNNT2, TNNI3, ACTC1, and DES. We describe a pediatric proband with fatal restrictive cardiomyopathy associated with septal hypertrophy and compound heterozygosity for TNNC1 mutations (NM_003280: p.A8V [c.C23T] and p.D145E [c.C435A]). This association between restrictive cardiomyopathy and TNNC1 mutations was strengthened by prospective observations on the second pregnancy in the family which revealed, in the presence of the same TNNC1 genotype, prenatally diagnosed hypertrophic cardiomyopathy which evolved into restrictive cardiomyopathy, heart failure and death at the age of 9 months. Contrary to previous reports, family and population analyses showed that each of the TNNC1 variants was not pathogenic when present alone. Our results (i) confirm that genetic backgrounds of hypertrophic cardiomyopathy and restrictive cardiomyopathy overlap and (ii) indicate that TNNC1 is a likely novel gene for autosomal recessive restrictive cardiomyopathy. © 2016 Wiley Periodicals, Inc.

show abstract

Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects

Cited by 168 publications

References 26 publications

Intermediate Filament Diseases: Desminopathy

Intermediate Filament Diseases: Desminopathy

Patologia do bloqueio atrioventricular na cardiomiopatia por depósito de desmina

Evidence for troponin C (TNNC1) as a gene for autosomal recessive restrictive cardiomyopathy with fatal outcome in infancy

Contact Info

Product

Resources

About