Congenital Muscular Dystrophy Associated with Familial Junctional Epidermolysis Bullosa Letalis

Doriguzzi, C.; Palmucci, L.; Mongini, Tiziana; Bertolotto, Antonio; Maniscalco, Mauro; Chiado'-Piat, Loredana; Am, Zina; Bundino, S

doi:10.1159/000116993

Cited by 19 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23 A homozygous insertion close to the IF-binding domain of plectin has been linked to epidermolysis bullosa simplex-muscular dystrophy in at least one patient who presented with marked desmin accumulations in muscle tissue and severe cerebral atrophy. 15 Combined with other case reports of brain atrophy associated with epidermolysis bullosa simplex, 24,25 this suggests that perturbations of the plectin/IF interactions due to plectin mutations or IF mutations can lead to neurological pathology.…”

Section: Implications For If Disorganization In Axdmentioning

confidence: 77%

Plectin Regulates the Organization of Glial Fibrillary Acidic Protein in Alexander Disease

Tian

Gregor

Wiche

et al. 2006

The American Journal of Pathology

View full text Add to dashboard Cite

Alexander disease (AxD) is a rare but fatal neurological disorder caused by mutations in the astrocytespecific intermediate filament protein glial fibrillary acidic protein (GFAP). Histologically, AxD is characterized by cytoplasmic inclusion bodies called Rosenthal fibers (RFs), which contain GFAP, small heat shock proteins, and other undefined components. Here, we describe the expression of the cytoskeletal linker protein plectin in the AxD brain. RFs displayed positive immunostaining for plectin and GFAP, both of which were increased in the AxD brain. Co-localization, co-immunoprecipitation, and in vitro overlay analyses demonstrated direct interaction of plectin and GFAP. GFAP with the most common AxD mutation, R239C (RC GFAP), mainly formed abnormal aggregates in human primary astrocytes and murine plectin-deficient fibroblasts. Transient transfection of full-length plectin cDNA converted these aggregates to thin filaments, which exhibited diffuse cytoplasmic distribution. Compared to wild-type GFAP expression, RC GFAP expression lowered plectin levels in astrocytoma-derived stable transfectants and plectin-positive fibroblasts. A much higher proportion of total GFAP was found in the Triton X-insoluble fraction of plectin-deficient fibroblasts than in wild-type fibroblasts. Taken together, our results suggest that insufficient amounts of plectin, due to RC GFAP expression, promote GFAP aggregation and RF formation in AxD.

show abstract

Section: Implications For If Disorganization In Axdmentioning

confidence: 77%

Plectin Regulates the Organization of Glial Fibrillary Acidic Protein in Alexander Disease

Tian

Gregor

Wiche

et al. 2006

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Additionally, some patients present with systemic involvement (e.g., gastroenterological, dental, urogenital and cardiac) [ 13 , 14 , 15 ]. A few individuals with EBS-MD show myasthenic features, such as fatigability, ptosis, dysphagia or nasal speech [ 7 , 16 , 17 ]. However, these features were not investigated systematically and additional tests, such as SF-EMG had previously only been performed in a single case.…”

Section: Discussionmentioning

confidence: 99%

Four Individuals with a Homozygous Mutation in Exon 1f of the PLEC Gene and Associated Myasthenic Features

Mroczek

Durmuş

Töpf

et al. 2020

Genes

View full text Add to dashboard Cite

We identified the known c.1_9del mutation in the PLEC gene in four unrelated females from consanguineous families of Turkish origin. All individuals presented with slowly progressive limb-girdle weakness without any dermatological findings, and dystrophic changes observed in their muscle biopsies. Additionally, the neurological examination revealed ptosis, facial weakness, fatigability, and muscle cramps in all four cases. In two patients, repetitive nerve stimulation showed a borderline decrement and a high jitter was detected in all patients by single-fiber electromyography. Clinical improvement was observed after treatment with pyridostigmine and salbutamol was started. We further characterize the phenotype of patients with limb-girdle muscular dystrophy R17 clinically, by muscle magnetic resonance imaging (MRI) features and by describing a common 3.8 Mb haplotype in three individuals from the same geographical region. In addition, we review the neuromuscular symptoms associated with PLEC mutations and the role of plectin in the neuromuscular junction.

show abstract

“…Electron microscopic analysis of MD-EBS muscle revealed that the most prominent ultrastructural feature was a striking disorganization in myofibrils and sarcomeres. Clinical description of patient 3 has been reported previously (7). Briefly, this patient, born from nonconsanguineous healthy parents, is a 29-yr-old male with epidermolysis bullosa and a severe, slowly progressive, muscle disease.…”

Section: Methodsmentioning

confidence: 99%

“…The major clinical subtypes of EBS have been associated with genetic defects in specific domains of keratins K5 and K14 that result in abnormal organization of the keratin network and cell disruption (2)(3)(4). Autosomal recessive forms of EBS associated with extracutaneous diseases, such as muscular dystrophy, have also been reported (MIM 226670) (5)(6)(7)(8). Similar to dominant EBS, the intraepidermal cleavage localizes within the basal keratinocytes.…”

Section: Introductionmentioning

confidence: 99%

Defective expression of plectin/HD1 in epidermolysis bullosa simplex with muscular dystrophy.

Gache¹,

Chavanas²,

Lacour³

et al. 1996

J. Clin. Invest.

217

142

View full text Add to dashboard Cite

Epidermolysis bullosa simplex with muscular dystrophy (MD-EBS) is a disease characterized by generalized blistering of the skin associated with muscular involvement. We report that the skin of three MD-EBS patients is not reactive with antibodies 6C6, 10F6, or 5B3 raised against the intermediate filament-associated protein plectin. Immunofluorescence and Western analysis of explanted MD-EBS keratinocytes confirmed a deficient expression of plectin, which, in involved skin, correlated with an impaired interaction of the keratin cytoskeleton with the hemidesmosomes. Consistent with lack of reactivity of MD-EBS skin to plectin antibodies, plectin was not detected in skeletal muscles of these patients. Impaired expression of plectin in muscle correlated with an altered labeling pattern of the muscle intermediate filament protein desmin. A deficient immunoreactivity was also observed with the monoclonal antibody HD121 raised against the hemidesmosomal protein HD1. Furthermore, immunofluorescence analysis showed that HD1 is expressed in Z-lines in normal skeletal muscle; whereas this expression is deficient in patient muscle. Colocalization of HD1 and plectin in normal skin and muscle, together with their impaired expression in MD-EBS tissues, strongly suggests that plectin and HD1 are closely related proteins. Our results therefore provide strong evidence that, in MD-EBS patients, the defective expression of plectin results in an aberrant anchorage of cytoskeletal structures in keratinocytes and muscular fibers leading to cell fragility.

show abstract

Congenital Muscular Dystrophy Associated with Familial Junctional Epidermolysis Bullosa Letalis

Cited by 19 publications

References 22 publications

Plectin Regulates the Organization of Glial Fibrillary Acidic Protein in Alexander Disease

Plectin Regulates the Organization of Glial Fibrillary Acidic Protein in Alexander Disease

Four Individuals with a Homozygous Mutation in Exon 1f of the PLEC Gene and Associated Myasthenic Features

Defective expression of plectin/HD1 in epidermolysis bullosa simplex with muscular dystrophy.

Contact Info

Product

Resources

About