SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A report on 89 cases of proximal Spinal Muscular Atrophy with observations on the clinical features, criteria of classification and modes of inheritance. The various forms into which SMA is divided probably represent a single disease that may begin at any age and may vary in severity, due, as a rule, to an autosomal recessive gene.
Explore the source record for details and available documents.
Spinal muscular atrophy (S.M.A.) type I (Infantile werdnig - Hoffmann Disease) was found in 4:1,600 (1:400) infants of the Egyptian Karaite community. This group constitutes a representative sample of the Egyptian Karaite community in Israel, which numbers at present somewhat more than 7,000. The community existed as a religious and reproductive isolate for over 10 centuries. The very high gene frequency, 0.05 for the autosomal recessive gene of S.M.A. type I, is probably the result of genetic drift.
Single fiber electromyography ( SFEMG ) of the extensor digitorum communis muscle was performed on 20 patients with either myopathic limb girdle syndromes ( LGS ) or chronic spinal muscular atrophy ( CSMA ) to assess its value in the differential diagnosis of these disorders. Neurologic examinations (muscle biopsies, standard electromyography, or both) were reviewed in 16 patients and resulted in diagnosing LGS in 11 patients and CSMA in 5 patients. In four patients, discordance between EMG and biopsy, or mixed features of myopathy and neuropathy in either test, resulted in an indeterminate diagnosis. Two groups were discerned from SFEMG , one with higher fiber density, jitter, and percentage of abnormal pairs consistent with neuropathy and another with lower values consistent with myopathy. In all 16 patients, SFEMG confirmed the initial diagnosis, and in the four patients with indeterminate diagnoses, SFEMG suggested diagnoses of LGS in two patients and CSMA in two patients. Single fiber electromyography may be a useful diagnostic aid in the differential diagnosis of myopathic LGS and CSMA .
DNA was recovered from sections of muscle biopsies of 20 spinal muscular atrophy (SMA) patients fixed on microscopic slides and stored from one to 20 years at room temperature. Microsatellite DNA markers tightly linked to the SMA locus were amplified using the polymerase chain reaction (PCR) to obtain specific amplified products. The procedure was successful in all cases, and allowed prenatal diagnosis in one at-risk pregnancy. In our hands this procedure is quick, sensitive and reproducible.
The critical region containing the spinal muscular atrophy (SMA) gene is flanked by the 5q11-q13 markers, D5S435 and D5S557, as determined by linkage analysis. Here we present the results of an analysis of a Dutch SMA family with the multicopy microsatellite marker CMS1. A crossover is revealed in the critical SMA region. We conclude that at least one of the CMS1 subloci maps proximal to the SMA gene. This reduces the minimal SMA region from approximately 1.4 Mb to 600-700 kb.
Glucose tolerance is reduced in patients suffering from neurogenic muscular atrophies. In a group of 20 patients with myatrophic lateral sclerosis the extent of atrophy correlated significantly with the decrease in glucose tolerance. Creatinine excretion was used as a measure of functioning muscle mass. Insulin secretion was not reduced, on the contrary, it was strongly pronounced in these cases. The observations are not explained by a decrease in distribution volume of glucose. By testing glucose tolerance, functions of sceletal muscles are examined at the same time. In evaluating the results, the functioning muscle mass has to be taken into account.
The majority of patients with chronic infantile and juvenile forms of spinal muscular atrophy survive to adult life. Forty-four patients have been reviewed at an average of 17 years after diagnosis. The subdivision of patients into four groups, based on the maximal physical function developed by the individual, correlates well with the onset and severity of secondary deformity of the limbs and spine. This information allows anticipation of the problems and plans for their treatment to be made from early childhood. After analysis of the orthotic and surgical treatment received by these patients, a specific programme of care is recommended for each of the functional groups.
A clinical-genealogical and electromyographic investigation of 142 patients with spinal muscular atrophies demonstrated a heterogeneous nature of spinal amyotrophies. A group of amyotrophies was specified as determined by the degeneration of only motor cells of the anterior corns. This group includes Werdnig-Hoffmann's infantile spinal amyotrophy, late childhood spinal amyotrophy, Kugelberg-Welander's juvenile amyotrophy, and late distal spinal amyotrophy. The group of spinal neural amyotrophies is made up of the clinical variants which are characterized by the parallel involvement of spinal motor cells and their axons. Spinal neural amyotrophies include the autosomal-recessive childhood and the autosomal-dominant juvenile variants.
Spinal Muscular Atrophy Type I (SMA I) is the most severe form of SMA. It presents in infancy and without treatment death occurs by 2 years. Treatments in use address respiratory and nutritional issues but even with aggressive treatment death is still likely in childhood. Thus their use is not obligatory. However, pediatric respirologists must be willing and comfortable at presenting all treatment options, including the option of palliative care, to families and then supporting the family's choice. Whatever the chosen treatment regimen, decision making is difficult for families. Support and help must be provided from the time of presentation till death by a knowledgeable and compassionate team.
The mutation that underlies the autosomal recessive disorder spinal muscular atrophy (SMA) is located on chromosome 5q13. Recent studies show that SMA patients frequently have deletions and rearrangements in this region compared to normal controls. During the isolation of candidate cDNAs for the disease, we identified a sequence that shows high homology to the THE-1 retrotransposon gene family. Using YAC fragmentation techniques, we have refined the localization of this sequence to the domain known to show instability in SMA patients. The implication of these results for the mechanism of the mutation in SMA is discussed.
Kennedy syndrome is a late-onset, bulbar-spinal type of muscular atrophy, with X-linked recessive inheritance. The characteristic features of the disease become prominent in the 4-5th decades: proximal muscle wasting and weakness, bulbar signs, fasciculations in skeletal muscles, subtle signs of endocrine dysfunction, such as gynaecomastia or testicular atrophy. The electrophysiological examinations are the keypoint to the diagnosis. Electroneurography shows normal conduction velocity in peripheral nerves, but the sensory nerves usually show axonal degeneration, which causes only very mild or subclinical neurological deficits. Electromyography shows chronic anterior horn cell degeneration in skeletal muscles. Molecular genetic diagnosis was introduced in 1991, when on abnormal expansion of CAG repeat was found in the first exon of the androgen receptor gene on chromosome X with a frequency of 100% in the affected population. Since the progression is very slow and these patients can expect a normal life span, it is essential to distinguish this syndrome from other, often more severe diseases, such as ALS. There is no proven therapy for Kennedy's disease yet. This is the first case of Kennedy's disease published in Hungary.
Approximately 94% of spinal muscular atrophy (SMA) patients lack both copies of SMN1 exon 7. We report our SMA genetic testing experience (total 1281 cases), using SMA linkage analysis (32 families), SMA diagnostic testing by PCR-RFLP (restriction fragment length polymorphism) to detect the homozygous absence of SMN1 exon 7 (and exon 8) (533 cases), and an assay to determine copy number of SMN1 exon 7 (SMN1 gene dosage analysis) (716 cases). SMN1 gene dosage analysis is used for SMA carrier testing as well as for the confirmation of a heterozygous SMN1 deletion in symptomatic individuals who do not lack both copies of SMN1. We conclude that comprehensive SMA testing, including SMN1 deletion analysis, SMN1 gene dosage analysis, and linkage analysis, offers the most complete evaluation of SMA patients and their families.
OBJECTIVES: This study evaluated muscular atrophy in the hemiplegic limbs by assessing the muscle volume of the thighs in stroke patients. DESIGN: Muscle volume of the bilateral thighs was determined by computed tomographic scanning in 50 hemiplegic patients after stroke. RESULTS: The average muscle volume in the hemiplegic side was significantly lower than that in the nonhemiplegic side. When the patients were divided into the two groups aged <65 yr old and >/=65 yr, age-dependent reduction in the muscle volume was significant only in the nonhemiplegic side. In addition, the ratio of the muscle volume in hemiplegic side to that in non-hemiplegic side was lower in the younger group than in the older group, with close to significance (P = 0.07). Muscle volume in both hemiplegic and nonhemiplegic sides correlated positively with Barthel index and negatively with patient age. CONCLUSION: Muscle volume decreases in the hemiplegic side in stroke patients.
OBJECTIVE: To assess the efficacy of phenylbutyrate (PB) in patients with spinal muscular atrophy in a randomized, double-blind, placebo-controlled trial involving 10 Italian centers. METHODS: One hundred seven children were assigned to receive PB (500 mg/kg/day) or matching placebo on an intermittent regimen (7 days on/7 days off) for 13 weeks. The Hammersmith functional motor scale (primary outcome measure), myometry, and forced vital capacity were assessed at baseline and at weeks 5 and 13. RESULTS: Between January and September 2004, 107 patients aged 30 to 154 months were enrolled. PB was well tolerated, with only one child withdrawing because of adverse events. Mean improvement in functional score was 0.60 in the PB arm and 0.73 in placebo arm (p = 0.70). Changes in the secondary endpoints were also similar in the two study arms. CONCLUSIONS: Phenylbutyrate was not effective at the regimen, schedule, and duration used in this study.
Herein we describe a family with X-linked spinal and bulbar muscular atrophy (SBMA or Kennedy's disease), an adult onset neuromuscular disease characterized by slow progression, predominant proximal and bulbar muscle weakness. One frequent association is the appearance of gynecomastia. This disorder was previously shown to be linked to the locus DXYS1 on the proximal long arm of the X chromosome. Recently, a report implicated a mutation at the N-terminus of the androgen receptor gene involving amplification of CAG repeats as the cause of X-linked SBMA. We studied this region of the androgen receptor in a kindred clinically suspected but not confirmed of having X-linked SBMA by the polymerase chain reaction (PCR) followed by Southern analysis and DNA sequencing. The mutated allele was found to have an increased number of 51 CAG repeats confirming the clinical diagnosis of SBMA. Normal individuals revealed 23 repeat numbers within the normal range, while another unrelated X-linked SBMA patient had an enlarged CAG repeat region. The carrier or disease status could be established or confirmed in 12 individuals of this family on the basis of detecting normal and disease alleles reflected by the number of CAG repeats.
The clinical and neuropathological findings of spinal muscular atrophy (SMA) in Holstein-Friesian calves are described in four females and one male from a dairy farm composed of 150 cows and 2 breeding bulls. Locomotion difficulties started at the age of 15 days, and progressed to paraparesis and tetraparesis in 2 weeks. Signs consistent with denervation were revealed with electromyography. The neuropathological examination showed degeneration and loss of motor neurons in the spinal cord, together with astrocytosis. Among the remaining motor neurons were ghost cells and neurons filled with accumulations of straight filaments measuring 10-12 nm in diameter, which were strongly immunoreactive with antibodies produced against phosphorylated neurofilaments. Degenerating cells in SMA did not stain with the method of in situ labelling of nuclear DNA fragmentation and did not show c-Jun immunoreactivity. This feature contrasts with the in situ labelling of DNA breaks of apoptotic cells and with the strong c-Jun immunoreactivity restricted to dying cells during the whole process of naturally occurring cell death in the developing central nervous system. These features suggest that cell death in SMA differs from programmed cell death during normal development, and that pathological cell death in SMA should not be considered as a mere persistence or reactivation of normally occurring developmental cell death.
In the period 1998-2000 almost all new cases of childhood spinal muscular atrophy (SMA) in addition to those from our database were studied for possible deletion of SMN gene (exons 7 a 8) and NAIP (exons 5 a 6). We correlated the size of deletion with the type, course and the onset of disease. The most informative for diagnosis was deletion of SMN. NAIP was deleted only in 18% of all cases, usually in SMA1 (in only 2 cases of SMA2). The molecular genetics permits to come back to previously posed question about the extremely frequent intrafamilial variability in SMA families. The problem became more clear due to our knowledge on telomeric and centromeric copies, as well as various genes and paragenes involved in SMA region. In the premolecular era we postulated the gender influence on course of the disease, which is particularly evident in mild SMA form 3b. Interestingly, presently we and some others detected deletion similar to those in the patients among the clinically healthy siblings. Those siblings are mostly females. The other problem, byproduct of molecular genetic, is the occurrence of SMN deletion in some disorders till now considered entirely different from SMA, e.g., arthrogryposis, congenital hypomyelinating neuropathies of newborn.