Biomedical subjects

M de Visser

Publications and source records attributed to M de Visser.

At least 55 records · Page 3Linked to original sources

PubMed2000

[The heartache of muscular dystrophy].

Duchenne and Becker muscular dystrophy are caused by a mutation in the dystrophin gene, located on the short arm of the X chromosome. Three so called dystrophinopathy patients, a women aged 54 and two men aged 23 and 21 years, suffered from a severe dilated cardiomyopathy. Such a cardiomyopathy can develop in both carriers and patients. In addition, it is often more important for prognosis than muscle weakness. For these two reasons it is important to screen both groups for (early) cardiological abnormalities. If these are present, regular follow-up is necessary to start timely therapy. When cardiological investigations yield normal results, it is advised to screen carriers with a five-year interval. Dystrophinopathy patients should be checked every year, because the cardiomyopathy sometimes develops and deteriorates over a short period of time. Patients with dilated cardiomyopathy and with a positive family history for dilated cardiomyopathy, muscle weakness or high serum creatine kinase activity should be screened for a mutation in the dystrophin gene.

Adult↗

PubMed2000

Mutation analysis of the entire mitochondrial genome using denaturing high performance liquid chromatography.

In patients with mitochondrial disease a continuously increasing number of mitochondrial DNA (mtDNA) mutations and polymorphisms have been identified. Most pathogenic mtDNA mutations are heteroplasmic, resulting in heteroduplexes after PCR amplification of mtDNA. To detect these heteroduplexes, we used the technique of denaturing high performance liquid chromatography (DHPLC). The complete mitochondrial genome was amplified in 13 fragments of 1-2 kb, digested in fragments of 90-600 bp and resolved at their optimal melting temperature. The sensitivity of the DHPLC system was high with a lowest detection of 0.5% for the A8344G mutation. The muscle mtDNA from six patients with mitochondrial disease was screened and three mutations were identified. The first patient with a limb-girdle-type myopathy carried an A3302G substitution in the tRNA(Leu(UUR)) gene (70% heteroplasmy), the second patient with mitochondrial myopathy and cardiomyopathy carried a T3271C mutation in the tRNA(Leu(UUR)) gene (80% heteroplasmy) and the third patient with Leigh syndrome carried a T9176C mutation in the ATPase6 gene (93% heteroplasmy). We conclude that DHPLC analysis is a sensitive and specific method to detect heteroplasmic mtDNA mutations. The entire automatic procedure can be completed within 2 days and can also be applied to exclude mtDNA involvement, providing a basis for subsequent investigation of nuclear genes.

Adenosine Triphosphatases↗

PubMed2000

Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B).

LGMD1B is an autosomal dominantly inherited, slowly progressive limb girdle muscular dystrophy, with age-related atrioventricular cardiac conduction disturbances and the absence of early contractures. The disease has been linked to chromosome 1q11-q21. Within this locus another muscular dystrophy, the autosomal dominant form of Emery-Dreifuss muscular dystrophy (AD-EDMD) has recently been mapped and the corresponding gene identified. AD-ADMD is characterized by early contractures of elbows and Achilles tendons and a humero-peroneal distribution of weakness combined with a cardiomyopathy with conduction defects. The disease gene of AD-EDMD is LMNA which encodes lamins A/C, two proteins of the nuclear envelope. In order to identify whether or not LGMD1B and AD-EDMD are allelic disorders, we carried out a search for mutations in the LMNA gene in patients with LGMD1B. For this, PCR/SSCP/sequencing screening was carried out for the 12 exons of LMNA on DNA samples of individuals from three LGMD1B families that were linked to chromo-some 1q11-q21. Mutations were identified in all three LGMD1B families: a missense mutation, a deletion of a codon and a splice donor site mutation, respectively. The three mutations were identified in all affected members of the corresponding families and were absent in 100 unrelated control subjects. The present identification of mutations in the LMNA gene in LGMD1B demonstrates that LGMD1B and AD-EDMD are allelic disorders. Further analysis of phenotype-genotype relationship will help to clarify the variability of the phenotype observed in these two muscular dystrophies.

Alleles↗

PubMed2000

Oral pulsed high-dose dexamethasone for myositis.

To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Six patients responded. Side effects were mild. At follow-up five responders were still in remission, without medication. Pulsed high-dose dexamethasone seems beneficial in myositis. A larger, prednisone-controlled trial is justified to analyze long-term efficacy.

Administration, Oral↗

PubMed2000

Sarcoglycanopathies in Dutch patients with autosomal recessive limb girdle muscular dystrophy.

Within a group of 76 sporadic/autosomal recessive limb girdle muscular dystrophy (LGMD) patients we tried to identify those with LGMD type 2C-E. Muscle biopsy specimens of 40 index patients, who had 22 affected sibs, were analyzed immuno-histochemically for the presence of three subunits: alpha-, beta-, and gamma-sarcoglycans. Abnormal sarcoglycan expression was established in eight patients, with six affected sibs. In one patient gamma-sarcoglycan was absent, and both alpha- and beta-sarcoglycans were reduced. In the remaining seven patients gamma-sarcoglycan was (slightly) reduced, and alpha- and beta-sarcoglycans were absent or reduced. By DNA sequencing mutations were detected in one of the three sarcoglycan genes in all eight cases. Three patients had mutations in the alpha-, three in the beta-, and two in the gamma-sarcoglycan gene. The patients with sarcoglycanopathy comprised the more severely affected cases (P=0.04). In conclusion, sarcoglycanopathy was identified in 23 % (14/62) of the autosomal recessive LGMD patients.

Adolescent↗

PubMed2000

Extension of the clinical range of facioscapulohumeral dystrophy: report of six cases.

Consensual diagnostic criteria for facioscapulohumeral dystrophy (FSHD) include onset of the disease in facial or shoulder girdle muscles, facial weakness in more than 50% of affected family members, autosomal dominant inheritance in familial cases, and evidence of myopathic disease in at least one affected member without biopsy features specific to alternative diagnoses. Six patients did not meet most of these criteria but were diagnosed as FSHD by DNA testing, which showed small EcoRI fragments on chromosome 4q. Their clinical signs and symptoms and results of auxiliary investigations are reported. The patients presented with foot extensor, thigh, or calf muscle weakness. None of them had apparent facial weakness, only one complained of weakness in the shoulders, none had a positive family history. Expert physical examination, however, showed a typical facial expression, an abnormal shoulder configuration on lifting the arms, or scapular winging. This raised the suspicion of FSHD, whereupon DNA analysis was done. In conclusion, the clinical expression of FSHD is much broader than indicated by the nomenclature. The possibility to perform DNA tests is likely to greatly expand the clinical range of FSHD.

Adult↗

PubMed1999

Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in The Netherlands: a cohort study.

BACKGROUND: Carriers of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) may show muscle weakness or dilated cardiomyopathy. Studies focusing on skeletal-muscle involvement were done before DNA analysis was possible. We undertook a cross-sectional study in a population of definite carriers to estimate the proportion and to assess the clinical profile of carriers with symptoms. We also assessed a possible correlation between genotype and phenotype. METHODS: Carriers of DMD and BMD, aged 18-60 years, were traced through the files of the central register kept at the Department of Human Genetics in Leiden, Netherlands. For each carrier who agreed to participate a medical history was taken, and muscle-strength assessment by hand-held dynamometry and manual muscle testing and cardiological assessment were done. FINDINGS: 129 carriers of muscular dystrophy (85 DMD, 44 BMD) participated in the study. In 90 women from 52 (70%) families, 37 different mutations were found. 28 (22%) women had symptoms. 22 (17%) had muscle weakness, varying from mild to moderately severe. Muscle weakness was found in carriers of DMD and BMD, but dilated cardiomyopathy was found only in seven (8%) carriers of DMD, of whom one had concomitant muscle weakness. There was an unexpectedly high proportion of left-ventricle dilation (18%). No genotype-phenotype correlation was found. INTERPRETATION: Clinical manifestation of muscle weakness, dilated cardiomyopathy, or both can be found in about a fifth of carriers of DMD and BMD. If left-ventricle dilation is taken into account, the proportion of carriers with symptoms is even higher, amounting to 40%.

Adolescent↗

PubMed1999

Impact of neurologic signs and symptoms on functional status in peripheral neuropathies.

OBJECTIVE: To determine whether the Neurologic Disability Score (NDS), the Neuropathic Symptom Score (NSS), and the Medical Research Council (MRC) "sumscore" are reliable, and to determine whether they provide information regarding the functional status of patients with peripheral neuropathies. METHODS: The authors analyzed homogeneity of the frequently used outcome measures in 97 patients using Cronbach's alpha coefficient and corrected item-total correlations. Their association with functional status (sickness impact profile and modified Rankin score) was analyzed univariately with Pearson's and Spearman's correlation coefficients, and multivariately with linear regression analysis. RESULTS: The NDS and MRC scales were homogeneous (range of Cronbach's alpha, 0.81 to 0.97) compared with the NSS scales (range, 0.20 to 0.63). The correlation patterns between neurologic signs and symptoms and functional status ranged from 0.13 to 0.65. Multivariate linear regression analyses showed that 40% or less of patients' functional status could be explained by the three tested outcome measures. CONCLUSION: The NDS and MRC are reliable measures, but these measures do not correlate with measures of functional status.

Activities of Daily Living↗

PubMed1999

Disability and functional assessment in former polio patients with and without postpolio syndrome.

OBJECTIVES: To compare perceived health problems and disability in former polio subjects with postpolio syndrome (PPS) and those without postpolio syndrome (non-PPS), and to evaluate perceived health problems, disability, physical performance, and muscle strength. DESIGN: Cross-sectional survey; partially blinded data collection. SUBJECTS: One hundred three former polio subjects, aged 32 to 60yrs. This volunteer sample came from referrals and patient contacts. Criterion for PPS: new muscle weakness among symptoms. MAIN OUTCOME MEASURES: Nottingham Health Profile (NHP), adapted D-code of the International Classification of Impairments, Disabilities and Handicaps, performance test, and muscle strength assessment. RESULTS: PPS subjects (n = 76) showed higher scores (p < .001) than non-PPS subjects (n = 27) within the NHP categories of physical mobility, energy, and pain. On a 16-item Polio Problems List, 78% of PPS subjects selected fatigue as their major problem, followed by walking outdoors (46%) and climbing stairs (41%). The disabilities of PPS subjects were mainly seen in physical and social functioning. No differences in manually tested strength were found between patient groups. PPS subjects needed significantly more time for the performance test than non-PPS subjects and their perceived exertion was higher. Perceived health problems (NHP-PhysMobility) correlated significantly with physical disability (r = .66), performance-time (r = .54), and muscle strength (r = .38). With linear regression analysis, 54% of the NHP-PhysMobility score could be explained by the performance test (time and exertion), presence of PPS, and muscle strength, whereas strength itself explained only 14% of the NHP-PhysMobility score. CONCLUSIONS: PPS subjects are more prone to fatigue and have more physical mobility problems than non-PPS subjects. In former polio patients, measurements of perceived health problems and performance tests are the most appropriate instruments for functional evaluation.

Activities of Daily Living↗

PubMed1999

Late onset polio sequelae: disabilities and handicaps in a population-based cohort of the 1956 poliomyelitis outbreak in The Netherlands.

OBJECTIVE: To investigate the prevalence of new neuromuscular symptoms, disabilities, and handicaps in a group of polio survivors. DESIGN: A self-constructed health questionnaire about neuromuscular complaints and disability and handicap levels during the stable period after recovery from polio and at present. SUBJECTS: Three hundred fifty subjects, derived from the 1,784 polio cases registered during the 1956 polio outbreak in The Netherlands. RESULTS: Respondents totaled 260 (74%), 27 of whom denied or did not recall having had paralytic poliomyelitis. The remaining 233 subjects comprised the study group (mean age, 44yrs; range, 39 to 77; SD = 6.3). Frequency of all neuromuscular complaints at present time was significantly higher than that during the stable period after polio (range in p of .001 to .004). Fifty-eight percent of cases reported an increase in muscle weakness in comparison with muscle condition during the stable period. Fifty-six percent reported an increase in disabilities, mainly a restriction in gait functions. Fifty-three percent reported increased handicaps with regard to occupation and social integration, and there was an increased need for adaptive measures and devices. CONCLUSION: Nearly 60% of a sample of Dutch survivors of the 1956 polio outbreak experience late onset polio sequelae, resulting in increased severity of disabilities and handicaps.

Adult↗

PubMed1999

Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy.

A cross-sectional study in a cohort of DNA proven carriers of Duchenne (DMD) and Becker (BMD) muscular dystrophy was undertaken with the following objectives: (1) to estimate the frequency of electrocardiographic (ECG) and echocardiographic abnormalities; (2) to establish the proportion of carriers with dilated cardiomyopathy and (3) to assess possible associations between dilated cardiomyopathy and genotype. One hundred and twenty nine DMD and BMD carriers, aged 18-60 years, were traced through the files of the central register kept at the department of Human Genetics in Leiden. Investigations included full medical history, physical examination, ECG and two-dimensional and M-mode echocardiographic examination. Forty-seven percent had ECG changes. Thirty-six percent (DMD 41%, BMD 27%) had at least one abnormality as is usually found in the male patients. Echocardiographic examination was abnormal in 36% (DMD 38%, BMD 34%). Dilated cardiomyopathy was found in seven DMD carriers (8%), and in none of BMD carriers. In addition, 18% had left ventricle dilatation (DMD 19%, BMD 16%). Only 38% had a completely normal investigation of the heart. We found no association between genotype and cardiac manifestations. Our study underlines that cardiac involvement is part of the dystrophinopathies. Carriers should be told about the increased risk of this complication when asking genetic advice. It also implicates that a complete cardiological evaluation should be performed at least once in all carriers. If left ventricle dilatation or dilated cardiomyopathy is present a yearly follow up is needed, in order to start timely therapy.

Adolescent↗

PubMed1999

A diagnostic fluorescent marker kit for six limb girdle muscular dystrophies.

The autosomal progressive muscular dystrophies which are grouped together under the term limb girdle muscular dystrophies (LGMD) are diseases characterized by a progressive impairment of the proximal limb muscles and myopathic changes on electromyogram and muscle biopsy. Eight independent purely recessive genetic entities have been recognized in this group of diseases by genetic localization or causative gene identification. We have developed fluorescent genetic markers bracketing six of these loci (LGMD2A-LGMD2F). The marker loci were genotyped in 96 LGMD2 families leading to genetic definition of 25 of them either with a high likelihood or with a suggested localization (7 LGMD2A, 5 LGMD2B, 4 LGMD2C, 4 LGMD2D, 2 LGMD2E and 3 LGMD2F). In addition, 18 families were excluded for all six tested loci; for 45 of the 53 remaining families at least one exclusion could be demonstrated. This kit, which makes the rapid genetic testing of LGMD2 families possible, may be useful in a diagnostic process.

Chromosome Mapping↗

PubMed1999

Calpainopathy-a survey of mutations and polymorphisms.

Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive disorder characterized mainly by symmetrical and selective atrophy of the proximal limb muscles. It derives from defects in the human CAPN3 gene, which encodes the skeletal muscle-specific member of the calpain family. This report represents a compilation of the mutations and variants identified so far in this gene. To date, 97 distinct pathogenic calpain 3 mutations have been identified (4 nonsense mutations, 32 deletions/insertions, 8 splice-site mutations, and 53 missense mutations), 56 of which have not been described previously, together with 12 polymorphisms and 5 nonclassified variants. The mutations are distributed along the entire length of the CAPN3 gene. Thus far, most mutations identified represent private variants, although particular mutations have been found more frequently. Knowledge of the mutation spectrum occurring in the CAPN3 gene may contribute significantly to structure/function and pathogenesis studies. It may also help in the design of efficient mutation-screening strategies for calpainopathies.

Amino Acid Sequence↗

PubMed1999

Bethlem myopathy: a slowly progressive congenital muscular dystrophy with contractures.

Bethlem myopathy is an early-onset benign autosomal dominant myopathy with contractures caused by mutations in collagen type VI genes. It has been reported that onset occurs in early childhood. We investigated the natural course of Bethlem myopathy in five previously published kindreds and two novel pedigrees, with particular attention to the mode of onset in 23 children and the progression of weakness in 36 adult patients. Our analysis shows that nearly all children exhibit weakness or contractures during the first 2 years of life. Early features include diminished foetal movements, neonatal hypotonia and congenital contractures which are of a dynamic nature during childhood. The course of Bethlem myopathy in adult patients is less benign than previously thought. Due to slow but ongoing progression, more than two-thirds of patients over 50 years of age use a wheelchair.

Activities of Daily Living↗

PubMed1998

Computed tomographic study of the skeletal musculature of the lower body in 45 postpolio patients.

Muscle computed tomography (CT) and muscle strength assessment of the pelvic girdle and leg muscles were performed in 32 postpolio patients experiencing new muscle weakness, and in 13 postpolio patients with stable neuromuscular condition. Muscles of the postpolio patients experiencing new muscle weakness showed significantly more CT scan abnormalities as compared with the stable postpolio patients. No other features discriminative of symptomatic postpolio patients were found. In individual patients, muscle CT scan evaluation is a useful adjunct to muscle strength assessment.

Adult↗

PubMed1998

Limb girdle muscular dystrophy: a pathological and immunohistochemical reevaluation.

Ninety-seven muscle biopsies from 81 limb girdle muscular dystrophy (LGMD) patients [32 autosomal recessive (AR), 15 autosomal dominant (AD), 34 sporadic] were morphologically reevaluated. Sarcoglycan analysis was done in 37 available muscle biopsies of AR and sporadic patients. Chi-square tests were used to analyze the relation between abnormalities in AR/sporadic versus AD cases. Eighty percent of the muscle biopsies showed a predominantly dystrophic pattern, 20% showed myopathic changes, and 17% of these also had neurogenic changes. Muscle histology was not significantly different between AR/sporadic and AD LGMD; however, the observed abnormalities were more pronounced in the AR/sporadic group. Collections of inflammatory cells were observed in 25% and 10% of the AR/sporadic and AD group, respectively. Sarcoglycanopathy was diagnosed in 25% of the AR and sporadic patients of the 37 families tested. We conclude that the histological picture of AR/sporadic and AD LGMD is essentially the same, and sarcoglycanopathy constitutes an important part of the AR/sporadic patients.

Cytoskeletal Proteins↗

PubMed1998

Genetic heterogeneity in Miyoshi-type distal muscular dystrophy.

Miyoshi-type distal muscular dystrophy (MMD) is an autosomal recessively inherited progressive disorder. The putative locus of MMD is linked to the limb-girdle muscular dystrophy 2B locus on chromosome 2p12-14. In this study three of four MMD pedigrees show non-linkage to the region spanned by D2S134-D2S358-D2S145 on chromosome 2p, indicating genetic heterogeneity. A genome wide screen was performed to identify loci linked to MMD. In two non-chromosome 2-linked families, a 23 cM region on chromosome 10 segregated with MMD.

Adult↗

PubMed1998

A novel gamma-sarcoglycan mutation causing childhood onset, slowly progressive limb girdle muscular dystrophy.

Limb girdle muscular dystrophy is a heterogeneous group of disorders. One autosomal recessive subtype, LGMD2C, has been linked to chromosome 13, and is caused by gamma-sarcoglycan deficiency in muscle. This report describes a novel missense mutation identified in a large consanguineous Dutch family with LGMD. This mutation leads to reduction of gamma-sarcoglycan, and gives rise to a childhood-onset, slowly-progressive dystrophy.

Adolescent↗