PubMed Health⌕ Search

Biomedical subjects

M Vainzof

Publications and source records attributed to M Vainzof.

At least 73 records · Page 4Linked to original sources
PubMed1993

Intrafamilial variability in dystrophin abundance correlated with difference in the severity of the phenotype.

In Duchenne muscular dystrophy, the progression of the disease is always severe and predictable, while in Becker dystrophy there is a wide variability (intra and inter familial) in the severity of the phenotype. We report here a family in which the proband, who is currently 15 years old, is showing a severe DMD progression, while his affected maternal uncle, aged 29, has a more benign course, compatible with BMD. No DNA deletion was detected in both patients. Dystrophin analysis through immunofluorescence and western blotting showed a negative pattern in the youngest patient and a positive one in the oldest. Apparently, this is the first report on intrafamilial variability in dystrophin abundance correlated with a difference in the severity of the phenotype.

Adolescent↗
PubMed1993

Sarcolemmal distribution of abnormal dystrophin in Xp21 carriers.

Some Becker muscular dystrophy carriers, related to patients with specific DNA deletions, demonstrate both normal and abnormally sized dystrophin bands through qualitative Western blot analysis. The purpose of the present investigation was to assess the sarcolemmal distribution of the altered dystrophin in such carriers. Fibres expressing the normal or deleted dystrophin were identified using specific antibodies which reacted with epitopes from within the deleted region. No negative fibres or patchy immunostaining could be seen when sections from four carriers were labelled with either antibodies (C-terminal and corresponding to the deleted region), although a significant amount of abnormal dystrophin was present in their muscle (as seen on blots). Thus, we were able to confirm that in a proportion of the myonuclei, the defective allele was present on the active X chromosome. Our results suggest that the two types of nuclei were randomly distributed, resulting in normal and abnormal dystrophin molecules which were so intimately mixed that dystrophin-incompetent fibres could not be distinguished in the skeletal muscle from the Xp21 carriers.

Adult↗
PubMed1993

Is the maintainance of the C-terminus domain of dystrophin enough to ensure a milder Becker muscular dystrophy phenotype?

The severe Duchenne muscular dystrophy (DMD) and the more benign Becker type (BMD) are allelic conditions, controlled by a defective gene at Xp21, caused by the absence (DMD) or a defect in quantity or quality (BMD) of the protein dystrophin. It has been suggested that the C-terminus domain of dystrophin is fundamental to ensure the proper protein sub-cellular localization and function. We wish to report our dystrophin findings in 4 among 142 DMD patients studied for DNA deletions and dystrophin analysis. Although they have a severe clinical course, a positive dystrophin immunofluorescence pattern was seen using C-terminal antibody, and a dystrophin band of reduced molecular weight (corresponding to their DNA deletions), but which maintained the C-terminus was seen through Western blot (WB). Based on these findings, we suggest that in order to partially maintain its function, resulting in a milder phenotype, dystrophin may carry large internal deletions but in addition to the C-terminus, the region encompassing both the N-terminus and the proximal region of the rod domain cannot be absent. Therefore, the prognosis of a Becker phenotype in a young patient should be done with caution if based only on the presence or not of dystrophin.

Adolescent↗
PubMed1993

Genetic heterogeneity for Duchenne-like muscular dystrophy (DLMD) based on linkage and 50 DAG analysis.

Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive (AR) muscular dystrophy which presents a clinical course indistinguishable from the Xp21 Duchenne muscular dystrophy or DMD. Recently, Othmane et al., based on a linkage study with 13q12 markers in 3 highly inbred DLMD families from Tunisia, suggested that the gene for this myopathy lies in the pericentromeric region of chromosome 13q. It is unknown if there is genetic heterogeneity causing the DLMD phenotype. Therefore, the aim of the present report is to describe the results of linkage analysis in 4 Brazilian DLMD families with 13q12 markers (D13S115 and D13S120), which were also tested for 50DAG. It was possible to exclude the 13q gene at theta = 0.10 as responsible for the DLMD phenotype in our families using both 13q12 markers, if the lod scores of each family were added up. Interestingly, 3 families were deficient for 50 DAG while one showed a positive pattern for this glycoprotein. Therefore, these results suggest: a) the DLMD phenotype is caused by more than one recessive gene; b) a gene, not located at 13q, causes deficiency of 50 DAG as a primary or secondary defect.

Brazil↗
PubMed1993

No evidence of genetic heterogeneity in Brazilian facioscapulohumeral muscular dystrophy families (FSHD) with 4q markers.

The gene responsible for facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant neuromuscular condition, has been mapped to chromosome 4. Until recently, the two closest available markers were D4S139 and D4S163 but a new marker (p13E-11) which recognizes de novo rearrangements in isolated cases of FSHD characterized by shorter EcoRI fragments has been now identified. Linkage analysis in FSHD families with p13E-11 shows that usually a smaller fragment segregates with the disease gene among the affected individuals from each genealogy. In the present paper, we report the results from linkage analysis with the marker loci D4S163 and D4S139 in 6 FSHD families and with p13E-11 in these and in 6 other additional Brazilian families (total of 12). The results from such analysis do not suggest genetic heterogeneity for FSHD in our population. In 11 out of the 12 families studied with p13E-11, a shorter specific EcoRI band was found to segregate in all affected patients from each genealogy. In one family, the normal individuals had a smaller EcoRI fragment than the affected ones. The size of the EcoRI fragments detected with p13E-11 varied from 13.5 to 29 kb but was constant within each genealogy. Our results suggest that the use of the marker p13E-11 for preclinical and prenatal diagnosis should be done only in families in which it is possible to identify the fragments segregating among the affected individuals.

Adolescent↗
PubMed1993

Cosegregation of schizophrenia with Becker muscular dystrophy: susceptibility locus for schizophrenia at Xp21 or an effect of the dystrophin gene in the brain?

A family is reported in which four of five adult patients with Becker muscular dystrophy (BMD) also have schizophrenia or related spectrum disorders. Although the estimated lod scores are not sufficient to conclude the existence of linkage between BMD and schizophrenia, it is suggested that there may be an association between these two disorders. Two alternative hypotheses are proposed to explain such an association: (1) the existence of a susceptibility locus for schizophrenia and spectrum disorders on the short arm of the X chromosome at Xp21; (2) that these psychiatric disorders may result from an abnormality in the expression of the dystrophin gene in the brain.

Adult↗
PubMed1993

Evidence of genetic heterogeneity in the autosomal recessive adult forms of limb-girdle muscular dystrophy following linkage analysis with 15q probes in Brazilian families.

The autosomal recessive limb-girdle muscular dystrophies (LGMD) represent a heterogeneous group of diseases which may be characterised by one or more autosomal loci. A gene at 15q has recently been found to be responsible for a mild form of LGMD in a group of families from the isolated island of Réunion, now classified as LGMD2. Based on results of eight out of 11 large Brazilian LGMD families of different racial background (which were informative for the closest available probe to the LGMD2 gene), we confirmed linkage to the LGMD2 gene at 15q in two of these families and exclusion in six others. These data provide the first evidence of genetic heterogeneity for the autosomal recessive limb-girdle muscular dystrophies.

Brazil↗
PubMed1992

A deletion including the brain promoter of the Duchenne muscular dystrophy gene is not associated with mental retardation.

A total of 161 unrelated Duchenne (DMD) and Becker muscular dystrophy (BMD) patients were screened for deletions in the brain promoter region of the dystrophin gene. Southern blot analysis using a probe for the brain promoter detected a deletion in this region in only one of the DMD families, in a patient with normal intelligence. This deletion also included the promoter of the muscle-type dystrophin and the exons encoding the actin-binding and part of the spectrin-like domains. Our data suggest that deletions in the brain promoter region are rare in DMD and are compatible with normal intelligence.

Adult↗
PubMed1992

A model to estimate the expression of the dystrophin gene in muscle from female Becker muscular dystrophy carriers.

The purpose of the present investigation was to assess the possibility of building a model to estimate, through dystrophin western blotting analysis, the expression of the DMD/BMD gene in muscle from heterozygotes. Dystrophin was analysed by mixing in increasing proportions (from 0% to 100%) aliquots of solubilised muscle from BMD patients with a qualitatively abnormal dystrophin and a normal male control. The intensity of the abnormal bands, which could be detected starting with 20% of muscle from the BMD patient, increased progressively according to the affected muscle concentration. In five obligate BMD carriers, two dystrophin bands were observed (corresponding to the products from the X bearing the normal and the BMD alleles), even among those with normal serum enzyme activities. Surprisingly, in the four obligate BMD carriers related to patients in whom an additional dystrophin fragment of 250 kd was present (two of them with raised serum enzymes), this band could not be seen, suggesting that the stability or the mechanism responsible for the synthesis of abnormal dystrophin products differs in heterozygotes compared to affected patients.

Adult↗
PubMed1991

Apparent association of mental retardation and specific patterns of deletions screened with probes cf56a and cf23a in Duchenne muscular dystrophy.

A total of 162 Duchenne (DMD) patients and two girls with a DMD phenotype were analysed for deletions in the central region of the dystrophin gene in order to determine if there was a correlation between mental retardation (MR) and the pattern of deletion. Approximately 43% of the patients studied had deletions with two dystrophin cDNAs, cf23a and cf56a, and among 148 patients who were mentally assessed, 50% were mentally retarded. The average IQ in the group of patients with DNA deletions did not differ significantly from those patients with no detectable deletions. However, six unrelated DMD boys with MR showed an identical pattern of deletion. Our observations in the group of patients who had detected DNA deletions suggest that exon 52 of the dystrophin gene may be functionally significant in the manifestation of MR: 70% (19/27) of patients with a deletion of this exon were mentally retarded, whereas only 38% (15/39) of MR patients had deletions not involving exon 52. This difference was statistically significant.

Chromosome Deletion↗
PubMed1991

Screening of male patients with autosomal recessive Duchenne dystrophy through dystrophin and DNA studies.

Previously we estimated that about 2.5-4% of isolated male patients diagnosed as Duchenne dystrophy (DMD) may have the autosomal recessive form (AR-DMD). Such cases can be distinguished from X-linked DMD through the analysis of dystrophin. Fifty DMD patients from 47 families were investigated for dystrophin and DNA deletions. Based on our results, we estimate that the frequency of AR-DMD may be about 8-12% among male patients diagnosed as DMD in whom X-linked inheritance could not be confirmed through pedigree data, serum enzymes in female relatives or DNA studies. Such an estimate must be confirmed in a larger sample; however, it shows the importance of assessing dystrophin in all patients diagnosed as DMD in whom X-linked inheritance cannot be proved, since the distinction between these 2 forms has implications for genetic counseling.

Consanguinity↗
PubMed1991

Familial occurrence of Duchenne dystrophy through paternal lines in four families.

In a survey of 454 families with patients affected with Duchenne muscular dystrophy (DMD) we have found 4 genealogies with 2 or more affected patients who were related through paternal lines. In 1 of these families, 2 affected cousins showed different DNA deletions suggesting 2 independent mutations; in the other 2, in which only the propositus could be studied DNA deletions were also detected in the dystrophin gene. In the last one, with 3 affected patients, no DNA deletions were detected but immunohistochemical study of muscle biopsies showed a negative dystrophin pattern typical of DMD. Although one of these families might have occurred by chance, the probability of finding the other 3 in our sample of families with DMD patients constitutes a rare event. It is suggested that other mechanisms, such as the presence of transposable elements in other sites of the genome, could be responsible in some families, for a greater predisposition for the occurrence of pathogenic deletions, duplications or mutations.

Child↗
PubMed1991

Linkage analysis in families with autosomal recessive limb-girdle muscular dystrophy (LGMD) and 6q probes flanking the dystrophin-related sequence.

The clinical similarity with the X-linked muscular dystrophies and the uniqueness of the homology between the DMD-like and the 1.8 kb sequences at the carboxyterminal domain of the dystrophin gene led to the suggestion that this 6q sequence might be a strong candidate for one of the autosomal recessive muscular dystrophies. Thus, we tested, through linkage analysis, if 6q probes flanking the dystrophin-homologous sequence are linked to the gene responsible for limb-girdle dystrophy (LGMD). A total of 226 individuals (57 patients and 169 unaffected relatives) from 19 large unrelated Brazilian families was studied. Results of two-point analysis excluded linkage with MYB (6q22-23) and ESR (6q24-q27) at 8 = 0.10 and with TCP1 (6q25-q27) at 0 = 0.05, indicating that the LGMD gene is not in the 6q23-q27 region. Therefore, the dystrophin-homologue sequence is not the gene responsible for LGMD.

Chromosome Mapping↗