Deletion of the Dystrophin Muscle-Promoter Region Associated with X-Linked Dilated Cardiomyopathy

Muntoni, Francesco; Cau, Milena; Ganau, Antonello; Congiu, Rita; Arvedi, Giuseppina; Mateddu, Anna; Marrosu, Maria Giovanna; Cianchetti, Carlo; Realdi, Giuseppe; Cao, Antonio; Melis, Maria Paola

doi:10.1056/nejm199309233291304

Cited by 387 publications

(172 citation statements)

References 29 publications

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“…However, recent research findings implicate mutations in genes that encode structural proteins that support the contractile apparatus or anchor cardiac myocytes in the extracellular matrix as the fundamental defects in some idiopathic (primary) DC. 2,12,15 Cardiomyopathies have also been linked to point mutations or rearrangements of mitochondrial DNA resulting in defects in oxidative phosphorylation or fatty acid oxidation. 1 Although the primary biochemical abnormality that is responsible for initiating the structural and functional defects that culminate in death from dysrhythmia or predominately left-sided congestive heart failure in DCDP are unknown, the pathologic events that precede dilation of the left ventricle and atrium follow a defined pathway.…”

Section: Discussionmentioning

confidence: 99%

Dilated Cardiomyopathy of Doberman Pinschers: Retrospective Histomorphologic Evaluation of Heart from 32 Cases

et al. 1999

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Abstract. Dilated cardiomyopathy of Doberman Pinschers (DCDP) is a progressive disease often presenting with a history of episodic weakness and syncope, or with clinical signs of predominantly left-sided congestive heart failure. A systematic dissection and histomorphologic evaluation of the heart from 32 Doberman Pinschers with a clinical diagnosis of dilated cardiomyopathy revealed a highly specific location for the characteristic myocardial lesions. The lesions of DCDP were found only in the left ventricular free wall, and in 30 cases, the lesions were characterized by myofiber degeneration and atrophy, and replacement of myocardium by dense bundles of collagen and clusters of adipocytes. In the two remaining hearts, myofiber atrophy and degeneration were accompanied by collagen deposition, but not adipocytes. In stained longitudinal (base to apex) tissue sections of the left ventricle, the lesions of DCDP were usually apparent to the unaided eye; appearing as a central linear pale zone, aligned in the long axis of the ventricular free wall. The lesions did not contain inflammatory cell infiltrates and often involved Ͼ50% of ventricular wall.

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Section: Discussionmentioning

confidence: 99%

Dilated Cardiomyopathy of Doberman Pinschers: Retrospective Histomorphologic Evaluation of Heart from 32 Cases

et al. 1999

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“…20,[27][28][29][30] The clinical examination, laboratory tests and genetic analyses excluded the coexistence of other disorders including laminopathy or a mitochondrial disease. However, the lack of a muscle biopsy, due to refusal by the patient, does not allow us to conclude unequivocally that her cardiac phenotype is due to the CAV3 mutation.…”

Section: Discussionmentioning

confidence: 99%

Caveolin-3 T78M and T78K missense mutations lead to different phenotypes in vivo and in vitro

Traverso

Gazzerro

Assereto

et al. 2008

Laboratory Investigation

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Caveolins are the principal protein components of caveolae, invaginations of the plasma membrane involved in cell signaling and trafficking. Caveolin-3 (Cav-3) is the muscle-specific isoform of the caveolin family and mutations in the CAV3 gene lead to a large group of neuromuscular disorders. In unrelated patients, we identified two distinct CAV3 mutations involving the same codon 78. Patient 1, affected by dilated cardiomyopathy and limb girdle muscular dystrophy (LGMD)-1C, shows an autosomal recessive mutation converting threonine to methionine (T78M). Patient 2, affected by isolated familiar hyperCKemia, shows an autosomal dominant mutation converting threonine to lysine (T78K). Cav-3 wild type (WT) and Cav-3 mutations were transiently transfected into Cos-7 cells. Cav-3 WT and Cav-3 T78M mutant localized at the plasma membrane, whereas Cav-3 T78K was retained in a perinuclear compartment. Cav-3 T78K expression was decreased by 87% when compared with Cav-3 WT, whereas Cav-3 T78M protein levels were unchanged. To evaluate whether Cav-3 T78K and Cav-3 T78M mutants behaved with a dominant negative pattern, Cos-7 cells were cotransfected with green fluorescent protein (GFP)-Cav-3 WT in combination with either mutant or WT Cav-3. When cotransfected with Cav-3 WT or Cav-3 T78M, GFP-Cav-3 WT was localized at the plasma membrane, as expected. However, when cotransfected with Cav-3 T78K, GFP-Cav-3 WT was retained in a perinuclear compartment, and its protein levels were reduced by 60%, suggesting a dominant negative action. Accordingly, Cav-3 protein levels in muscles from a biopsy of patient 2 (T78K mutation) were reduced by 80%. In conclusion, CAV3 T78M and T78K mutations lead to distinct disorders showing different clinical features and inheritance, and displaying distinct phenotypes in vitro.

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“…tion [25,35,39,44,49,50], hence adding another phenotype of dystrophinopathy to the already known spectrum. Electrocardiographic (ECG) changes similar to those seen in DMD can be found in 41%-74% of BMD patients [7,11,12,23,45].…”

Section: Introductionmentioning

confidence: 99%

“…In recent years the correlation between cardiac involvement and the defect at the DNA level has been studied [11,23,25,32,40,45]. To date, several mutations have been described which may give rise to DCM.…”

Section: Introductionmentioning

confidence: 99%

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Evolution of cardiac abnormalities in Becker muscular dystrophy over a 13-year period

Hoogerwaard

Voogt

Wilde

et al. 1997

Journal of Neurology

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Deletion of the Dystrophin Muscle-Promoter Region Associated with X-Linked Dilated Cardiomyopathy

Cited by 387 publications

References 29 publications

Dilated Cardiomyopathy of Doberman Pinschers: Retrospective Histomorphologic Evaluation of Heart from 32 Cases

Dilated Cardiomyopathy of Doberman Pinschers: Retrospective Histomorphologic Evaluation of Heart from 32 Cases

Caveolin-3 T78M and T78K missense mutations lead to different phenotypes in vivo and in vitro

Evolution of cardiac abnormalities in Becker muscular dystrophy over a 13-year period

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