Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Muscular Atrophy”

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.

At least 739 records · Page 41Linked to original sources
PubMed2005

Detection of homozygous and heterozygous SMN deletions of spinal muscular atrophy in a single assay with multiplex ligation-dependent probe amplification.

OBJECTIVE: Spinal muscular atrophy(SMA), an autosomal recessive neuromuscular degeneration of the anterior horn cells of the spinal cord and brain stem, results in one of the most common diseases with muscle fatigue and atrophy. Most SMA cases including all the types are due to the homozygous deletion of at least exon 7 within the survival motor neuron 1 (SMN-1) gene. Although a "golden standard" assay (PCR with mismatch primer followed by enzyme digestion) is very reliable for the identification of homozygous SMN-1 deletion, the carrier detection of heterozygous SMN-1 deletion remains a challenge. METHODS: Some PCR-based gene dosage assays or multiplex PCR allow for the determination of the copy number of SMN-1 gene to identify heterozygous deletion, but these procedures are often time consuming and available on a limited clinical basis. Recently developed MLPA (multiplex ligation-dependent probe amplification) is an efficient procedure that can accurately analyze relative quantification to establish the copy number of the SMN gene. We performed a validation for simultaneous detection of homozygous SMN-1 deletions of SMA patients and heterozygous SMN-1 deletions of SMA carriers in a simple assay using a MLPA-SMA assay specific reagent. RESULTS: Six out of 20 patients with SMA were found to have homozygous SMN-1 deletion, confirmed by the PCR/digestion assay. All 4 parents of the children with SMA had heterozygous SMN-1 deletion, confirmed by an independent relative quantitative analysis. CONCLUSION: MLPA provides a simple, rapid and accurate method of simultaneously detecting homozygous deletions and heterozygous deletions in a single assay for both SMN-1 and SMN-2 genes.

Cyclic AMP Response Element-Binding Protein↗
PubMed1980

[Investigations of peripheral and central somatosensory pathways in peroneal muscular atrophy and Friedreich's heredoataxia (author's transl)].

Twenty-eight patients with peroneal muscular atrophy (PMA) have been investigated. Eighteen of them were affected by the Charcot-Marie-Tooth disease and three by Dejerine-Sottas disease. In these 21 cases the nerve conduction velocity (NCV) was decreased. Four patients presented the neuronal type of PMA, two cases showed sensory neuropathy of the neuronal type with ophthalmoplegia, and one case, PMA with ataxia, i.e., a myatrophic ataxia. In the neuronal type of PMA, including both cases with ophthalmophegia, the amplitudes of the sensory nerve action potentials were decreased, and the NCV was normal to slightly subnormal. In myatrophic ataxia NCV was decreased. In all cases with reduced NCV, the latencies of the spinal-evoked potentials (spinEP) and somatosensory-evoked potentials (ssEP) were prolonged. In the neuronal type of PMA, these latencies were normal. The central latencies (from thoracic and cervical level) were normal in all 28 patients with PMA of different types. Seventeen patients with Friedreich's heredoatazia have been investigated. In all except two cases, NCV was normal. The sensory nerve-action potentials markedly decreased or disappeared in all cases. The peripheral neurographic picture, accordingly, corresponds to that of patients with the neuronal type of PMA. The latencies of spinEP were normal. All patients with Friedreich's heredoatazia, however, showed prolonged latencies of ssEP. Calculating the central latencies as the difference between ssEP and spinEP latencies (cervical and thoracic) confirms that this is due to a slowing of the conduction velocity via the spinobulbar tracts.

Adolescent↗
PubMed2002

Correlation between SMN2 copy number and clinical phenotype of spinal muscular atrophy: three SMN2 copies fail to rescue some patients from the disease severity.

Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder that is characterized by degeneration of the anterior horn cells of the spinal cord, which leads to the axial and limb weakness associated with muscle atrophy. SMA is classified into three groups based on the clinical severity: type I (severe), type II (intermediate) and type III (mild). All three clinical subtypes of SMA are caused by mutations of the SMN1 gene. More than 95 % of SMA patients show homozygous deletion of SMN1. It is thought that SMN2, which is a highly homologous gene of SMN1, compensates for the SMN1 deletion to some degree. To clarify the relationship between SMN2 and the disease severity of SMA, we performed fluorescence-based quantitative polymerase chain reaction assay of the copy number of SMN2 in 27 patients (11 type I and 16 type II-III) homozygous for SMN1 deletion. The SMN2 copy number in type II-III patients was 3.1 +/- 0.3 (mean +/- SD), which is significantly higher than that observed in type I patients, 2.2 +/- 0.6 (P < 0.01). However, three of the 11 type I patients carried 3 SMN2 copies. A type I patient with 3 SMN2 copies was studied further. RT-PCR analysis of the patient showed a trace of full-length SMN2 mRNA species, but a large amount of the truncated SMN2 mRNA species lacking exon 7. In conclusion, SMN2 alleles are not functionally equivalent among SMA patients, although in general the SMN2 copy number is correlated with the severity of SMA. Genetic background influencing splicing mechanisms of the SMN2 gene may be more critical in some SMA patients.

Adolescent↗
PubMed1986

Electromyographic findings in different forms of infantile and juvenile proximal spinal muscular atrophy.

Quantitative electromyography (EMG) was performed in 223 infantile and juvenile cases of spinal muscular atrophy (SMA), which were classified into 3 groups: (A) form Ia, Werdnig-Hoffmann disease; (B) forms Ib and II, intermediate forms; and (C) form III, Kugelberg-Welander disease. The groups differed in the occurrence of spontaneous activity; only groups A and B showed spontaneous rhythmic firing of motor units, whereas in long-standing cases, pseudomyotonic volleys appeared. The parameters of individual motor unit potentials (MUPs) differed in the different forms of the disease. Group A showed, in addition to long potentials of high amplitude, some short and low amplitude potentials, and the histograms of amplitudes and durations were bimodal. In the long-standing cases, the values of these parameters were shifted to longer durations and higher amplitudes of motor unit potentials. However, in long-standing cases of the benign group C, the short, low potentials appeared as well as so-called linked potentials. In the very early stage of the disease, the children who were found to be suffering from chronic forms of SMA--both malignant (form Ib and II or benign group C)--had an EMG record that was slightly different from that of acute form Ia. Their EMG record shows more so-called "spinal" signs, particularly in the benign group C (Kugelberg-Welander disease). These increasing features of chronic anterior horn cell involvement followed a pattern of reinnervation and hypertrophy of muscle fibers. These phenomena were particularly seen in the benign group C. These findings indicate that in the early stage of SMA, the EMG not only has diagnostic, but also prognostic, value.

Action Potentials↗
PubMed2000

Spinal muscular atrophy type 1: A noninvasive respiratory management approach.

STUDY OBJECTIVE: To determine whether spinal muscular atrophy (SMA) type 1 can be managed without tracheostomy and to compare extubation outcomes using a respiratory muscle aid protocol vs conventional management. DESIGN: A retrospective cohort study. METHODS: Eleven SMA type 1 children were studied during episodes of respiratory failure. Nine children required multiple intubations. Along with standard treatments, these children received manually and mechanically assisted coughing to reverse airway mucus-associated decreases in oxyhemoglobin saturation. Extubation was not attempted until, most importantly, there was no oxygen requirement to maintain oxyhemoglobin saturation greater than 94%. After extubation, all patients received nasal ventilation with positive end-expiratory pressure. Successful extubation was defined by no need to reintubate during the current hospitalization. RESULTS: Two children have survived for 37 and 66 months and have never been intubated despite requiring 24-h nasal ventilation since 5 and 7 months of age, respectively. One other child underwent tracheostomy for persistent left lung collapse and inadequate home care, another for need for frequent readmission and intubation, and one child was lost to follow-up 3 months after successful extubation. The other six children have been managed at home for 15 to 59 (mean 30.4) months using nocturnal nasal ventilation after an episode of respiratory failure. The nine children were successfully extubated by our protocol 23 of 28 times. The same children managed conventionally were successfully extubated 2 of 20 times when not using this protocol (p < 0.001 by the two-tailed Fisher's Exact t Test). CONCLUSION: Although intercurrent chest colds may necessitate periods of hospitalization and intubation, tracheostomy can be avoided throughout early childhood for some children with SMA type 1.

Child, Preschool↗
PubMed2000

The relationship between SMN, the spinal muscular atrophy protein, and nuclear coiled bodies in differentiated tissues and cultured cells.

The spinal muscular atrophy protein, SMN, is a cytoplasmic protein that is also found in distinct nuclear structures called "gems." Gems are closely associated with nuclear coiled bodies and both may have a direct role in snRNP maturation and pre-RNA splicing. There has been some controversy over whether gems and coiled bodies colocalize or form adjacent/independent structures in HeLa and other cultured cells. Using a new panel of antibodies against SMN and antibodies against coilin-p80, a systematic and quantitative study of adult differentiated tissues has shown that gems always colocalize with coiled bodies. In some tissues, a small proportion of coiled bodies (<10%) had no SMN, but independent or adjacent gems were not found. The most striking observation, however, was that many cell types appear to have neither gems nor coiled bodies (e.g., cardiac and smooth muscle, blood vessels, stomach, and spleen) and this expression pattern is conserved across human, rabbit, and pig species. This shows that assembly of distinct nuclear bodies is not essential for RNA splicing and supports the view that they may be storage sites for reserves of essential proteins and snRNPs. Overexpression of SMN in COS-7 cells produced supernumerary nuclear bodies, most of which also contained coilin-p80, confirming the close relationship between gems and coiled bodies. However, when SMN is reduced to very low levels in type I SMA fibroblasts, coiled bodies are still formed. Overall, the data suggest that gem/coiled body formation is not determined by high cytoplasmic SMN concentrations or high metabolic activity alone and that a differentiation-specific factor may control their formation.

Animals↗
PubMed2002

Determinants of the interaction of the spinal muscular atrophy disease protein SMN with the dimethylarginine-modified box H/ACA small nucleolar ribonucleoprotein GAR1.

Deletion or mutation of the SMN1 (survival of motor neurons) gene causes the common, fatal neuromuscular disease spinal muscular atrophy. The SMN protein is important in small nuclear ribonucleoprotein (snRNP) assembly and interacts with snRNP proteins via arginine/glycine-rich domains. Recently, SMN was also found to interact with core protein components of the two major families of small nucleolar RNPs, fibrillarin and GAR1, suggesting that SMN may also function in the assembly of small nucleolar RNPs. Here we present results that indicate that the interaction of SMN with GAR1 is mediated by the Tudor domain of SMN. Single point mutations within the Tudor domain, including a spinal muscular atrophy patient mutation, impair the interaction of SMN with GAR1. Furthermore, we find that either of the two arginine/glycine-rich domains of GAR1 can provide for interaction with SMN, but removal of both results in loss of the interaction. Finally, we have found that unlike the interaction of SMN with the Sm snRNP proteins, interaction with GAR1 and fibrillarin is not enhanced by arginine dimethylation. Our results argue against post-translational arginine dimethylation as a general requirement for SMN recognition of proteins bearing arginine/glycine-rich domains.

Amino Acid Substitution↗
PubMed1988

Electrophysiological findings in childhood spinal muscular atrophies.

The aim of this study was to evaluate in indirect way through electrical activity of muscles and nerves the state of motoneuron in different forms of childhood spinal proximal muscular atrophies (SMA). The material comprised 454 cases of SMA type Ia (Werdnig-Hoffmann) types Ib + II (intermediate form) and type III (Kugelberg-Welander form). The quantitative EMG revealed the differences between different forms of SMA's in respect to spontaneous and volitional activity. The most unique phenomenon is the occurrence in SMA Ia form of rhythmic firing of motor unit (MUF) persisting during sleep. The comparison of duration, shape and amplitude of action potentials in acute severe form Ia and mild long-standing form III indicates the inability to increase the motor unit territory in form Ia as opposed to form III where most motoneurons have ability to enlarge their field. It was also stated that in the early stage of SMA the EMG has not only diagnostic but also prognostic value.

Adolescent↗
PubMed2004

[Quantitative analysis of SMN gene copies in spinal muscular atrophy].

OBJECTIVE: To study the genetic basis in the patients with clinical diagnosis of spinal muscular atrophy(SMA) but without survival motor neuron telomeric copy (SMN-T) deletion; the relationship between the SMN-C (centromeric) copies and the phenotype; and the distribution of SMN-C and SMN-T copies in the SMA patients, the carriers and the controls. METHODS: Quantitative PCR analysis of SMN-T and SMN-C copies were carried out in 45 patients, 25 consanguineous and 33 control individuals. The patients were identified by clinical manifestation and muscular pathology. Two internal standards of SMN-T and cystic fibrosis transmembrane conductance regulator (CFTR) were constructed. Nonradioactive and nonfluorescence-labelling competitive PCR were used. The numbers of SMN-T and SMN-C copies were determined by calculating the ratios of SMN-T/CFTR and SMN-C/CFTR. RESULTS: Quantitation of SMN-T gene copies in SMA patients revealed that nine cases of type I-III were homozygously deleted. Two cases of type III had only one copy and four cases of type III had two copies. SMA IV and other type cases had two copies. Nine cases of consanguineous individuals had one copy, but other 16 had two copies. All of the normal individuals had two copies. Analysis of SMN-C copies showed that SMA I had < or = 2 copies, II-III had < or = 3 copies, SMA IV and others had 0-3 copies, the consanguineous individuals and normal individuals had 0-3 copies. CONCLUSION: The number of copies determined by PCR quantitative assay of SMN-T is in accordance with the result of PCR qualitative assay of homozygous deletion. Quantitative assay of the number of copies can find out the cases and the carriers of heterozygous deletion. The SMA phenotype is related to the number of copies of SMN-C; the smaller the number of copies the patient has, the severer the patient's phenotype will be. The pathogenesis of SMA IV and other types of SMA may not relate to SMN gene.

Cyclic AMP Response Element-Binding Protein↗
PubMedDate not supplied

[Cervical collar therapy for juvenile muscular atrophy of distal upper extremity (Hirayama disease): results from 38 cases].

BACKGROUND: Juvenile muscular atrophy of distal upper extremity is a peculiar type of cervical myelopathy affecting young people characterized by localized amyotrophy in the forearm and hand that is initially progressive, and then stabilized in a few years. The anterior horn cell damage may be induced by forward displacement of the lower cervical dural sac and spinal cord on neck flexion. We proposed that the forward displacement was one of pathogenic factors, and reported that therapeutic intervention using a cervical collar in order to minimize neck flexion halted the progressive weakness in some patients. OBJECTIVE: To examine effectiveness of cervical collar treatment for this disease and to investigate clinical and radiological profiles that predict a favorable outcome before treatment. METHODS: Thirty-eight patients who had progressive illness within 5 years after onset underwent cervical collar therapy (treatment group). Forty-five patients in a previous case series without any therapeutic intervention made up a control group. The duration of progressive phase of illness was compared between the two groups. In the treatment group, the time interval from onset and the measurements of cervical cord atrophy and its flattening on neck flexion at the introduction of treatment by CT-myelography or MRI were analyzed with respect to prognosis. RESULTS: All the patients in the treatment group showed no further progression after introduction of treatment. The duration of the progressive period was shorter in the treatment group (mean 1.8 +/- 1.2 years) than in the control group (mean 3.2 +/- 2.3 years) (p < 0.005). In the treatment group, 15 of 31 patients within 2.5 years after the onset showed not only stabilization but also improvement of muscular weakness or cold paresis. Five of 7 patients who had no or mild cord atrophy at the introduction showed improvement after treatment. CONCLUSION: Cervical collar therapy induces a premature arrest of this disease. Improvement is expected in patients who have shorter duration of illness and have mild cord atrophy in a neutral neck position. Early diagnosis and therapeutic intervention may minimize the functional disability of young patients.

Adolescent↗
PubMed1994

The DNA diagnosis for bulbospinal muscular atrophy.

We showed the analysis of the androgen receptor gene in 6 patients with bulbospinal muscular atrophy (BSMA). Four of them had typical manifestations of Kennedy's disease, while the other 2 patients did not show androgen insensitive signs such as gynecomastia or testicular atrophy. Enlarged CAG repeats were found in 4 patients with typical Kennedy's disease and 1 patient without androgen insensitive signs. This fact suggests that the DNA diagnosis by analysis of the androgen receptor gene is very useful to distinguish Kennedy's disease from other forms of BSMA.

DNA↗
PubMed1977

Familial progressive bulbar-spinal muscular atrophy: case report with muscle biopsy study.

A case of familial progressive bulbar and spinal muscular atrophy was presented. The patient was a 59-year-old male with chief complaints of gait disturbance and nasal voice. His illness started at the age of 39 and very slowly progressed over 20 years. The clinical symptoms and signs were characterized by muscle weakness and atrophy due to lower motor neuron disease in the brain stem below the lower pons and the spinal cord. The electromyograms and muscle biopsy findings are basically neurogenic. In spite of the bulbar signs, the course of the disease is extremely slow. The diagnostic criteria was proposed after reviewing eight other cases reported in the literature.

Adult↗
PubMed1981

The pharyngo-laryngeal deficit in the acute form of infantile spinal muscular atrophy (Werdnig-Hoffmann disease).

The major complication in the acute form of infantile spinal muscular atrophy is the aspiration phenomenon, due to the pharyngo-laryngeal deficit. The radiographic findings of this deficit are characterized by epipharyngeal regurgitation, hypopharyngeal distention, good function of the cricopharyngeal sphincter and absence of epiglottic closure during the act of deglutition. The differential diagnosis of other neuromuscular entities is discussed in view of two documented radiographic cases.

Acute Disease↗
PubMed1990

[Postpolio late progressive muscular atrophy--clinical and epidemiologic analyses in 4 Japanese cases].

Four Japanese cases of postpolio progressive muscular atrophy (PPMA) of late onset were clinically studied to characterize their clinical features and discussed upon the epidemiologic viewpoint. Four male patients were included with mean age of 43.5 (30-59) years on examination, diagnosed as PPMA after the criteria by Alter (1982) and Dalakas (1986). All suffered from polio at age 10 month to 8 years (mean: 3y) between 1931 and 1957 with residual motor paresis in one limb or two. Twenty-eight to 55 (mean: 40.3) years later, subsequent muscle weakness and atrophy appeared in the limb seemingly unaffected by the initial polio attack. Marked fasciculations and occasional myalgias were noticed without sensory disturbance and bulbar as well as upper motor neuron signs. Laboratory examinations revealed moderate elevations of serum CK and protein content in SCF. No significant elevation of polio virus antibody titers was found in both serum and CSF. Electromyography showed neurogenic changes of various degrees by muscle tested. Muscle CT disclosed patchy distribution of atrophied muscles with fatty replacement in all extremities. Spinal cord MRI images were unremarkable. Scatters of small grouped atrophy and fiber type grouping were noticed on muscle biopsy specimens. These findings summarized in our cases are generally compatible with those of hereby reported PPMA cases. On reviewing the western literature and the great epidemic of polio around 1960 in Japan, an increasing number of patients with PPMA can be anticipated in near future; possibly in 10 years.

Adult↗