Cases reported "Muscular Dystrophies"

Filter by keywords:



Filtering documents. Please wait...

1/9. epidermolysis bullosa simplex associated with muscular dystrophy: phenotype-genotype correlations and review of the literature.

    BACKGROUND: epidermolysis bullosa simplex associated with muscular dystrophy (EBS-MD; OMIM# 226670) is an autosomal recessive disorder caused by genetic defects in the plectin gene. Because EBS-MD is relatively rare, and gene defects have been elucidated only in a limited number of patients, the precise phenotype-genotype correlations have not yet been fully elucidated. OBJECTIVE: The purpose of this study was to define clinical features of EBS-MD and to clarify its phenotype-genotype correlations. methods: Clinical, ultrastructural, immunohistochemical, and molecular features of 4 unrelated Japanese patients with EBS-MD were recorded. In addition, 6 cases with defined plectin gene mutations reported in the literature were reviewed. RESULTS: In skin of the EBS-MD patients, the blister formation always occurs just above the hemidesmosomes, and expression of plectin is absent or markedly reduced in all cases examined. All 10 patients, including 6 cases in the literature, showed generalized blistering at birth or soon thereafter, and experienced nail deformities. In addition, decayed teeth (5 cases), urethral strictures (3), mild palmoplantar hyperkeratosis (2), infantile respiratory complications (2), alopecia (1), and laryngeal webs (1) were present. All 8 patients who were older than 9 years demonstrated considerable muscle weakness, and the majority of them ended up being wheelchair bound. Among the 10 patients, 7 were products of consanguineous marriage, 9 have premature termination codon (PTC) mutations in both alleles of the plectin gene, and 7 cases were homozygous for the mutation. One patient who is homozygous for a 2719del9 in-frame deletion mutation that resulted in elimination of 3 amino acids, QEA, could still walk at the age of 46 and showed milder clinical severity. CONCLUSION: EBS-MD reveals clinical features not only characteristic of EBS and MD, but also other manifestations including urethral, dental, and respiratory complications. The majority of patients are products of consanguineous marriage and have homozygous plectin gene mutations. Whereas patients with PTC mutations in both alleles typically showed severe clinical features of EBS-MD and ended up being wheelchair bound, a homozygous patient for an in-frame deletion mutation showed positive, yet attenuated, plectin expression and milder clinical phenotype. Thus plectin immunofluorescence, combined with identification of the underlying plectin mutations, is of value in predicting the severity of the muscle involvement that occurs later in life of patients with EBS-MD.
- - - - - - - - - -
ranking = 1
keywords = bullosa
(Clic here for more details about this article)

2/9. Severe mucous membrane involvement in epidermolysis bullosa simplex with muscular dystrophy due to a novel plectin gene mutation.

    epidermolysis bullosa simplex with muscular dystrophy (OMIM 226670) is an autosomal recessive disorder caused by mutations of the human plectin gene on chromosome 8q24. Here, we report a 3-year-old girl, offspring of a consanguineous Lebanese family, who presented with skin blistering and recurrent episodes of severe respiratory distress necessitating tracheotomy at the age of 2 years. Repeated examination did not provide any evidence of muscle involvement. Indirect immunofluorescence analysis of a diagnostic skin biopsy with four different domain specific plectin antibodies showed a complete absence of plectin staining. mutation analysis revealed a novel homozygous single guanine insertion mutation (5588insG/5588insG) residing in the N-terminal part of exon 31 of the plectin gene. CONCLUSION: The complete lack of protein expression, which may be attributed to a nonsense-mediated plectin mRNA decay, is likely to cause muscular dystrophy and other multisystem involvement later in life.
- - - - - - - - - -
ranking = 14.145411912411
keywords = epidermolysis bullosa, epidermolysis, bullosa
(Clic here for more details about this article)

3/9. plectin deficient epidermolysis bullosa simplex with 27-year-history of muscular dystrophy.

    BACKGROUND: epidermolysis bullosa simplex associated with muscular dystrophy is caused by plectin deficiency. OBJECTIVE: To report clinical, immunohistochemical, ultrastructural and molecular features of a 52-year-old Japanese patient affected with this disease, whose muscular disease had been followed-up for 27 years. methods: We performed histopathological study, immunofluorescence, electron microscopic study and mutation detection analysis for plectin. RESULTS: The patient developed blisters and erosions followed by nail deformity on the traumatized regions from birth. The skin lesions were continuously developed to date. The histopathological study showed subepidermal blister. Electron microscopic study showed blister formation inside the basal cells at the level just above the attachment plaque of hemidesmosome. Immunofluorescence showed complete loss of staining to plectin. The mutation analysis using protein truncation test and dna sequencing revealed a C-to-T transition at nucleotide position 7006 of the plectin cDNA sequence, which lead a novel homozygous nonsense mutation (R2319X). CONCLUSION: From the above results, the diagnosis of epidermolysis bullosa simplex associated with muscular dystrophy was made. Slight muscular dystrophy was noticed at the age of 25 years. The muscular dystrophy gradually progressed and she could not walk at the age of 46 years. However, she can still breathe and swallow by herself. This is the patient of this disease with the longest follow-up, and may indicate the slow progress of muscular condition of this disease.
- - - - - - - - - -
ranking = 17.631764890514
keywords = epidermolysis bullosa, epidermolysis, bullosa
(Clic here for more details about this article)

4/9. Autosomal recessive epidermolysis bullosa simplex. Generalized phenotypic features suggestive of junctional or dystrophic epidermolysis bullosa, and association with neuromuscular diseases.

    With few exceptions, epidermolysis bullosa (EB) simplex is an autosomal dominant disorder characterized by rather localized and recurrent nonscarring blister formation; mucous membranes and other organs are usually uninvolved. Recently, two patients were described with an autosomal recessive form of EB simplex associated with muscular dystrophy. We now describe four additional patients with autosomal recessive EB simplex, three of whom had associated muscular dystrophy or congenital myasthenia gravis. These patients had generalized cutaneous findings, including milia, atrophic scarring, nail dystrophy, and scalp alopecia, which have been classically attributed to either junctional or dystrophic EB. Each patient had significant oral cavity involvement, and in two, marked growth retardation and anemia were also present. Our findings suggest that autosomal recessive EB simplex may be characterized by rather severe cutaneous and extracutaneous disease activity, and may be associated with at least two distinct neuromuscular diseases.
- - - - - - - - - -
ranking = 31.377176802925
keywords = epidermolysis bullosa, epidermolysis, bullosa
(Clic here for more details about this article)

5/9. epidermolysis bullosa simplex associated with muscular dystrophy with recessive inheritance.

    Epidermolysis bullosa with unusually severe clinical features was associated with progressive muscular dystrophy in two siblings. light and electron microscopic examination revealed an intraepidermal cleavage confirming that this mechanobullous disease belonged to the epidermolysis bullosa simplex group. This may represent a new disease entity inherited in an autosomal-recessive fashion.
- - - - - - - - - -
ranking = 4.4863529781028
keywords = epidermolysis bullosa, epidermolysis, bullosa
(Clic here for more details about this article)

6/9. epidermolysis bullosa simplex associated with muscular dystrophy: a new case.

    We report an infant with a rare form of epidermolysis bullosa simplex characterized by an autosomal recessive pattern of inheritance, severe cutaneous involvement, oral and nail lesions, associated with muscular dystrophy, and a poor prognosis, due to extracutaneous disease. In addition to the usual presentation of this disease, our patient had severe anemia, with immature circulating white cells, and bone marrow histology suggestive of a pre-leukemic state, a finding which has not before been reported in the literature.
- - - - - - - - - -
ranking = 4.2863529781028
keywords = epidermolysis bullosa, epidermolysis, bullosa
(Clic here for more details about this article)

7/9. Congenital muscular dystrophy associated with familial junctional epidermolysis bullosa letalis.

    A 20-year-old patient was born with epidermolysis bullosa and a severe, slowly progressive muscle disease. skin biopsy demonstrated junctional epidermolysis bullosa. Muscle biopsy demonstrated degenerative changes with increase in connective tissue, fibre size variability, rods and cytoplasmic bodies, central nuclei. In muscle biopsy dystrophin, chondroitin unsulphate, chondroitin 4-sulphate, chondroitin 6-sulphate, heparan sulphate, collagen III, collagen IV and VI, laminin, and fibronectin were normally distributed. This is the first report of the association of a form of congenital muscular dystrophy with junctional epidermolysis bullosa and, together with the previous reports of muscle involvement in epidermolysis bullosa simplex and dystrophica, it suggests the existence of a syndrome characterized by the contemporaneous presence of skin and muscle involvement.
- - - - - - - - - -
ranking = 27.890823824822
keywords = epidermolysis bullosa, epidermolysis, bullosa
(Clic here for more details about this article)

8/9. Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization.

    plectin is a widely expressed high molecular weight protein that is involved in cytoskeleton-membrane attachment in epithelial cells, muscle, and other tissues. The human autosomal recessive disorder epidermolysis bullosa with muscular dystrophy (MD-EBS) shows epidermal blister formation at the level of the hemidesmosome and is associated with a myopathy of unknown etiology. Here, plectin was found to be absent in skin and cultured keratinocytes from an MD-EBS patient by immunofluorescence and immunoprecipitation, suggesting that plectin is a candidate gene/protein system for MD-EBS mutation. The 14800-bp human plectin cDNA was cloned and sequenced. The predicted 518-kD polypeptide has homology to the actin-binding domain of the dystrophin family at the amino terminus, a central rod domain, and homology to the intermediate filament-associated protein desmoplakin at the carboxyl terminus. The corresponding human gene (PLEC1), consisting of 33 exons spanning >26 kb of genomic dna was cloned, sequenced, and mapped to chromosomal band 8q24. Homozygosity by descent was observed in the consanguineous MD-EBS family with intragenic plectin polymorphisms. Direct sequencing of PCR-amplified plectin cDNA from the patient's keratinocytes revealed a homozygous 8-bp deletion in exon 32 causing a frameshift and a premature termination codon 42 bp downstream. The clinically unaffected parents of the proband were found to be heterozygous carriers of the mutation. These results establish the molecular basis of MD-EBS in this family and clearly demonstrate the important structural role for plectin in cytoskeleton-membrane adherence in both skin and muscle.
- - - - - - - - - -
ranking = 17.431764890514
keywords = epidermolysis bullosa, epidermolysis, bullosa
(Clic here for more details about this article)

9/9. Novel compound heterozygous mutations in the plectin gene in epidermolysis bullosa with muscular dystrophy and the use of protein truncation test for detection of premature termination codon mutations.

    Absence of plectin, a large cytoskeleton-associated protein expressed in the skin and muscle, has been shown to underlie epidermolysis bullosa with muscular dystrophy (EB-MD), an autosomal recessive disorder (OMIM No. 226670). In the present study, we report the case of a patient who presented with neonatal blistering and late-onset muscular dystrophy with nail and tooth abnormalities, as well as severe mucocutaneous involvement including laryngeal webs and urethral strictures, features not previously reported in this syndrome. mutation detection, based on the use of heteroduplex analysis, revealed that the proband was a compound heterozygote for two plectin mutations, 4416delC/4359ins13, both resulting in premature termination codons in the plectin rod domain. Because these mutations, and the majority of those previously reported, reside within exon 32 of the plectin gene (PLEC1), we applied the protein truncation test (PTT) to screen for mutations in the two large 3' exons (nos. 32 and 33) of PLEC1, which together comprise approximately 75% of the coding region of the gene. PTT readily detected truncated polypeptides in the proband profiled in this study, as well as in a patient in whom we have previously identified premature termination codon mutations in exon 32. Thus, PTT provides a rapid and reliable strategy to identify premature termination codon mutations from genomic dna within PLEC1.
- - - - - - - - - -
ranking = 17.431764890514
keywords = epidermolysis bullosa, epidermolysis, bullosa
(Clic here for more details about this article)


Leave a message about 'Muscular Dystrophies'


We do not evaluate or guarantee the accuracy of any content in this site. Click here for the full disclaimer.