1,720,975 research outputs found
Morphological changes in late onset acid Maltase deficient patients with splicing gene mutation
No full textNeuronal Nitric Oxide Synthase (nNOS) activity and ultrastructural changes in caveolin-3 deficient muscle cause mechanical irritability.
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Characterization of a highly repeated DNA sequence family in five species of the genus Eulemur
No full textThe karyotypes of Eulemur species exhibit a high degree of variation, as a consequence of the Robertsonian fusion and/or centromere fission. Centromeric and pericentromeric heterochromatin of eulemurs is constituted by highly repeated DNA sequences (including some telomeric TTAGGG repeats) which have so far been investigated and used for the study of the systematic relationships of the different species of the genus Eulemur. In our study, we have cloned a set of repetitive pericentromeric sequences of five Eulemur species: E. fulvus fulvus (EFU), E. mongoz (EMO), E. macaco (EMA), E. rubriventer (ERU), and E. coronatus (ECO). We have characterized these clones by sequence comparison and by comparative fluorescence in situ hybridization analysis in EMA and EFU. Our results showed a high degree of sequence similarity among Eulemur species, indicating a strong conservation, within the five species, of these pericentromeric highly repeated DNA sequences. (C) 2001 Elsevier Science B.V. All rights reserved
The yield of molecular diagnosis is higher in severe (SCARMD, LGMD) than in milder (myopathy, high CK) phenotypes
No full textAdult acid maltase deficiency: an open trial with albuterol and branched- chain aminoacids
No full textGeneralized lysosome-associated membrane protein-2 defect explains multisystem clinical involvement and allows leukocyte diagnostic screening in Danon disease
Full text linkDanon disease, an X-linked dominant disorder, results
from mutations in the lysosome-associated
membrane protein-2 (LAMP2) gene and presents with
hypertrophic cardiomyopathy, skeletal myopathy,
and mental retardation. To investigate the effects of
LAMP2 gene mutations on protein expression in different
tissues, we screened LAMP2 gene mutations
and LAMP-2 protein deficiency in the skeletal muscle
of nine unrelated patients with hypertrophic cardiomyopathy
and vacuolar myopathy. We identified
three novel families (including one affected mother)
with unreported LAMP2 gene null mutations and
LAMP-2 protein deficiency in skeletal and myocardial
muscle, leukocytes, and fibroblasts. LAMP-2 protein
deficiency was detectable in various tissues, including
leukocytes, explaining the multisystem clinical involvement.
Skeletal muscle immunopathology
showed that mutant protein was not localized in the
Golgi complex, vacuolar membranes expressed sarcolemmal-
specific proteins, and the degree of muscle
fiber vacuolization correlated with clinical muscle involvement.
In our female patient, muscle histopathology
and LAMP-2 protein analysis was inconclusive,
indicating that diagnosis in females requires mutation
identification. The random X-chromosome inactivation
found in muscle and leukocytes excluded the
possibility that selective involvement of some tissues
in females is due to skewed X-chromosome inactivation.
Therefore, biochemical analysis of leukocytes
might be used for screening in male patients, but
genetic screening is required in females. (Am J Pathol
2006, 168:1309–1320; DOI: 10.2353/ajpath.2006.050646
Molecular and Muscle Pathology in a series of Caveolinopathy patients
No full textMutations in the caveolin-3 gene (CAV3) cause limb girdle muscular dystrophy (LGMD) type 1C (LGMD1C)
and other muscle phenotypes. We screened 663 patients with various phenotypes of unknown etiology, for
caveolin-3 protein deficiency, and we identified eight unreported caveolin-deficient patients (from seven
families) in whom four CAV3 mutations had been detected (two are unreported). Following our wide screening,
we estimated that caveolinopathies are 1% of both unclassified LGMD and other phenotypes, and demonstrated
that caveolin-3 protein deficiency is a highly sensitive and specific marker of primary caveolinopathy. This is the
largest series of caveolinopathy families in whom the effect of gene mutations has been analyzed for protein level
and phenotype.We showed that the same mutation could lead to heterogeneous clinical phenotypes and muscle
histopathological changes. To study the role of the Golgi complex in the pathological pathway of misfolded
caveolin-3 oligomers, we performed a histopathological study on muscle biopsies from caveolinopathy patients.
We documented normal caveolin-3 immunolabeling at the plasmalemma in some regenerating fibers showing a
proliferation of the Golgi complex. It is likely that caveolin-3 overexpression occurring in regenerating fibers
(compared with caveolin-deficient adult fibers) may lead to an accumulation of misfolded oligomers in the Golgi
and to its consequent proliferation
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