Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease)

McKoy, Godfrina; Protonotarios, Nikos; Crosby, Andrew H.; Tsatsopoulou, Adalena; Anastasakis, Aris; Coonar, Aman S.; Norman, Mark; Baboonian, C.; Jeffery, Steve; McKenna, William J.

doi:10.1016/s0140-6736(00)02379-5

Cited by 969 publications

(693 citation statements)

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“…The deletion of nucleotides 2157 and 2158 causes a frameshift and premature termination of translation 29 . Thus, the C-terminal domain of plakoglobin is shortened by 56 amino acid residues.…”

Section: Geneticsmentioning

confidence: 99%

Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare “disease of the desmosome” with multiple clinical presentations

2009

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Section: Geneticsmentioning

confidence: 99%

Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare “disease of the desmosome” with multiple clinical presentations

2009

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“…Several genetic loci have been reported to be associated with the disease and mutations in six genes have been identified: ryanodine receptor, plakoglobin, desmoplakin and recently transforming growth factor-β, plakophilin-2 and desmoglein. [9][10][11][12][13][14][15][16] Patients with mutations in the ryanodine receptor gene, also called ARVC2, are more prone to develop arrhythmias. 17 The recognition that ARVC is frequently familial and can cause arrhythmic death leads to the challenge to identify family members who are at risk.…”

Section: Discussionmentioning

confidence: 99%

Arrhythmogenic right ventricular cardiomyopathy: asymptomatic to life threatening as illustrated by the cases of two sisters

Otterspoor¹,

Reichert²,

Bhuiyan³

et al. 2007

NHJL

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Arrhythmogenic right ventricular cardiomyopathy: asymptomatic to life threatening as illustrated by the cases of two sisters Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder of unknown cause that is characterised by fibrofatty replacement, primarily of the right ventricular myocardium, which can lead to life-threatening arrhythmias. It is a disease with a very diverse phenotype. In the present article we describe two sisters, each with a different manifestation of this disorder. The first patient died suddenly at the age of 18 during exercise. Her 17-year-old sister did not have any abnormalities at first cardiac consultation, but a few years later she met several diagnostic criteria for ARVC and an internal cardioverter defibrillator was implanted. Genetic analysis identified a mutation in the plakophilin-2 (PKP2) gene. Cardiac evaluation of a third sister did not reveal any abnormalities and no mutation in the PKP2 gene was found. Thus, ARVC can vary in its clinical presentation, not only between siblings but also in time. This raises difficulties for the physician for diagnosis, treatment and followup. It is important for the physician involved to consider this disease in patients with palpitations and syncope, especially when there is a family history of ARVC or unexplained sudden death. (Neth Heart J 2007;15:348-53.)

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“…Only one pathogenic mutation in the gene encoding the other major desmosomal plaque protein, plakoglobin (JUP), has been reported [74]. A homozygous 2-base pair deletion, c. 2157delTG, was shown to be the cause of an autosomal recessive disorder involving heart, skin and hair abnormalities, known as Naxos disease (OMIM601214) which partially resembles the phenotype in plakoglobin-deficient transgenic mice [75].…”

Section: Plakoglobin Gene Mutation Causes Naxos Diseasementioning

confidence: 99%

Diseases of epidermal keratins and their linker proteins

Uitto

Richard

McGrath³

2007

Experimental Cell Research

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Epidermal keratins, a diverse group of structural proteins, form intermediate filament networks responsible for the structural integrity of keratinocytes. The networks extend from the nucleus of the epidermal cells to the plasma membrane where the keratins attach to linker proteins which are part of desmosomal and hemidesmosomal attachment complexes. The expression of specific keratin genes is regulated by differentiation of the epidermal cells within the stratifying squamous epithelium. Progress in molecular characterization of the epidermal keratins and their linker proteins has formed the basis to identify mutations which are associated with distinct cutaneous manifestations in patients with genodermatoses. The precise phenotype of each disease apparently reflects the spatial level of expression of the mutated genes, as well as the types and positions of the mutations and their consequences at mRNA and protein levels. Identification of specific mutations in keratinization disorders has provided the basis for improved diagnosis and subclassification with prognostic implications and has formed the platform for prenatal testing and preimplantation genetic diagnosis. Finally, precise knowledge of the mutations is a prerequisite for development of gene therapy approaches to counteract, and potentially cure, these often devastating and currently intractable diseases. KeywordsEpidermal keratins; intermediate filaments; epidermal differentiation; hemidesmosomes; desmosomes; genodermatoses; skin fragility; epidermolysis bullosa; epidermolytic hyperkeratosis; ichthyosis Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. BIOLOGY OF EPIDERMAL KERATINSKeratins NIH Public Access Author ManuscriptExp Cell Res. Author manuscript; available in PMC 2008 November 4. Published in final edited form as:Exp Cell Res. 2007 June 10; 313(10): 1995-2009. doi:10.1016/j.yexcr.2007.03.029. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript dimensional and highly dynamic cytoskeleton spanning between the nucleus and the cell membrane, where they are anchored by interactions with desmosomal and hemidesmosomal linker proteins (Fig. 1). This organization provides both structural stability and flexibility, and ensures the mechanical integrity of different epithelial tissues. Keratins are expressed as obligate heterodimers of acidic (type I) and basic (type II) proteins, which assemble, through a multi-step process, into intermediate filaments (Fig. 2). The genes encoding type I and type II keratins cluster on chromosomal regions 17q12-q21 and 12q11-q13, respectively. Keratin ...

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Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease)

Cited by 969 publications

References 28 publications

Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare “disease of the desmosome” with multiple clinical presentations

Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare “disease of the desmosome” with multiple clinical presentations

Arrhythmogenic right ventricular cardiomyopathy: asymptomatic to life threatening as illustrated by the cases of two sisters

Diseases of epidermal keratins and their linker proteins

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