Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked spinal and bulbar muscular atrophy (SBMA), a motor neuron disease associated with androgen insensitivity, is caused by androgen receptor gene mutations with an increased number of tandem CAG repeats in exon 1. We investigated the increased number of CAG repeats in androgen receptor genes of 19 SBMA patients and found that this correlated strongly with the age at onset of muscle weakness. Thus, SBMA is the first genetic disease in which a strong correlation between the degree of genetic abnormality (number of CAG tandem repeats) and clinical phenotypic expression is demonstrable. The results further indicate that androgen gene mutation is directly involved in the degeneration of motor neurons.
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PMID:Strong correlation between the number of CAG repeats in androgen receptor genes and the clinical onset of features of spinal and bulbar muscular atrophy. 146 83

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.
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PMID:Analysis of the CAG repeat region of the androgen receptor gene in a kindred with X-linked spinal and bulbar muscular atrophy. 146 23

We describe three families with X-linked recessive Charcot-Marie-Tooth (CMT) neuropathies. The disease phenotype in family 1 was characterized by infantile onset, weakness of lower legs, areflexia, pes cavus, and mental retardation (2 of 5 patients). The disease phenotype in families 2 and 3 was characterized by late onset, distal weakness, and normal intelligence. Hereditary spastic paraparesis was also present in the CMT patients of family 2. Thirty X-linked DNA markers were used for linkage studies. A maximum lod score of +3.48 was obtained by multipoint linkage analysis for the DXS16 locus mapped at Xp22.2 in family 1. In families 2 and 3, there was suggestion of linkage of Xq26 markers; the peak multipoint lod score for these 2 CMT families was 1.81, at DXS144. These results were suggestive of heterogeneity. The joint analysis including both regions (Xp22.2 and Xq26) provided evidence against homogeneity (chi 2 = 9.12, P less than 0.005).
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PMID:X-linked recessive Charcot-Marie-Tooth neuropathy: clinical and genetic study. 155 86

We performed a clinical study and linkage analysis on 278 subjects (66 affected) belonging to eight families with X-linked dominant Charcot-Marie-Tooth (CMT) neuropathy. This form affects 11.8% of CMT patients in Iowa. Motor nerve conduction velocities (MNCVs) were significantly slowed consistent with type 1 CMT. Fifty-six obligate carriers manifested mild distal weakness, localized areflexia, pes cavus, and slowing on MNCVs. Seven X-linked restriction fragment length polymorphisms mapping in the Xp11-q21 region were tested for linkage against CMT. Two-point linkage results showed the highest lod scores with PGK1, DXS159, and DXYS1. Multipoint linkage analysis excluded the CMT gene from being telomeric to either DXS14 or DXYS1, with over 1,000:1 odds. The highest location scores were at PGK1 and 1 cM proximal to DXS159.
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PMID:Mapping of the gene for X-linked dominant Charcot-Marie-Tooth neuropathy. 156 50

X-linked dystrophinopathy is the most common cause of isolated cases of myopathy in males. To investigate dystrophin abnormalities as a cause of myopathy in girls and women, we used dystrophin immunocytochemistry to study muscle biopsies from 505 girls and women with neuromuscular disease. Forty-six muscle biopsies showed a combination of fibers containing or lacking dystrophin; this mosaic immunostaining pattern denoted a carrier status. Twenty-one of 46 (45.6%) had a family history of Duchenne muscular dystrophy in males. Twenty-five of 46 (54.3%) were isolated cases, with no previous family history of neuromuscular disorder. The laboratory findings of the isolated cases were consistent with the familial cases; all showed myopathic histopathology and abnormal elevations of serum CK. The clinical presentations of the isolated cases varied but were consistent with the familial cases: 40% (10/25) of isolated cases showed proximal limb weakness before age 10, 24% (6/25) presented with myalgias or cramps, 24% (6/25) presented with incidental findings of grossly elevated CK levels, 8% (2/25) noted easy fatigue, and 4% (1/25) had slowly progressive proximal limb weakness beginning at age 45. From our data, the clinical criteria for consideration of an underlying dystrophinopathy in isolated female cases of myopathy are CK levels greater than 1,000 IU/l and myopathic histopathology. About 10% of the isolated cases of hyperCKemic myopathy (25/210) were proven by dystrophin analysis to have a dystrophinopathy as the cause of their disease (manifesting carriers of Duchenne dystrophy). However, we feel that this may be an underestimate. The correct diagnosis in these patients is imperative for appropriate genetic counseling to the patients and their families.
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PMID:Dystrophinopathy in isolated cases of myopathy in females. 157 51

We report 11 children with a homogeneous clinical syndrome affecting both sexes, characterized by weakness at birth, slowly improving course, weakness of all muscle groups, arreflexia, elevated blood creatine kinase, normal nerve conduction velocity, dystrophic changes on muscle biopsy, and diffuse periventricular cortical white-matter abnormalities with sparing of corpus callosum, internal capsule, and brain stem. We compare them to 48 other previously reported similar cases and designate them as altered myelin radiographic pattern congenital muscular dystrophy (CMD), which is the same as occidental CMD. We compare them to the other presently accepted phenotypes: progressive Fukuyama CMD, Walker-Warburg or cerebral-ocular CMD, and Santavuori or muscle-eye-brain CMD. We suggest that the different phenotypes are alleles of the same gene, which regulates or expresses a structural protein required for muscle integrity, myelination, and formation of the cortex. Such phenotypic diversity has been established for mutations of Xp21 in X-linked muscular dystrophies.
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PMID:Congenital muscular dystrophy with abnormal radiographic myelin pattern. 158 16

Three families presenting with X-linked recessive Charcot-Marie-Tooth neuropathies (CMT) were studied both clinically and genetically. The disease phenotype in family 1 was typical of CMT type 1, except for an infantile onset; two of five affected individuals were mentally retarded, and obligate-carrier females were unaffected. Families 2 and 3 showed distal atrophy with weakness, juvenile onset, and normal intelligence. Motor-nerve conduction velocities were significantly slowed, and electromyography data were consistent with denervation in affected CMT males in all three families. Thirty X-linked RFLPs were tested for linkage studies against the CMT disease loci. Family 1 showed tight linkage (recombination fraction [theta] = 0) to Xp22.2 markers DXS16, DXS143, and DXS43, with peak lod scores of 1.75, 1.78, and 2.04, respectively. A maximum lod score of 3.48 at DXS16 (theta = 0) was obtained by multipoint linkage analysis of the map DXS143-DXS16-DXS43. In families 2 and 3 there was suggestion of tight linkage (theta = 0) to Xq26 markers DXS86, DXS144, and DXS105, with peak lod scores of 2.29, 1.33, and 2.32, respectively. The combined maximum multipoint lod score of 1.81 at DXS144 (theta = 0) for these two families occurred in the map DXS10-DXS144-DXS51-DXS105-DXS15-DXS52++ +. A joint homogeneity analysis including both regions (Xp22.2 and Xq26-28) provided evidence against homogeneity (chi 2 = 9.12, P less than .005). No linkage to Xp11.12-q22 markers was observed, as was reported for X-linked dominant CMT and the Cowchock CMT variant. Also, the chromosomes 1 and 17 CMT loci were excluded by pairwise linkage analysis in all three families.
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PMID:Heterogeneity in X-linked recessive Charcot-Marie-Tooth neuropathy. 167 39

Duchenne muscular dystrophy (DMD) is an X-linked disease characterized by progressive muscle weakness and degeneration. Dystrophin is the product of the missing gene in this disorder. However, the cause of the dystrophic process is not understood. Transient muscle injury is normally seen after muscle exercise, and may be a necessary process in muscle growth and preservation. We, therefore, chose to evaluate the role of exercise in Duchenne dystrophy by studying the canine X-linked animal model (CXMD). These dogs also lack dystrophin and have clinical signs similar to humans. Exercise was initiated by electrical stimulation, and muscle metabolism was monitored with phosphorus magnetic resonance spectroscopy (P-MRS). Dogs with CXMD had abnormal muscle pathology and markedly elevated serum CK. The inorganic phosphate (Pi) to phosphocreatine (PCr) ratio was increased in CXMD dogs at rest compared with normal dogs (Pi/(Pi + PCr) = 0.166 +/- 0.054 for CXMD and 0.073 +/- 0.017 for normals, mean +/- SE). No changes in resting ATP, pH, phosphomonoesters (PME), and phosphodiesters (PDE) were seen. The mean Pi/(Pi + PCr) and pH values during stimulation were normal in the CXMD dogs. Two to three days after electrical stimulation, resting Pi/(Pi + PCr) ratios were significantly increased in the CXMD dogs (0.127 +/- 0.029 compared with 0.172 +/- 0.054, mean +/- SD). Normal dogs showed no increase in Pi/(Pi + PCr) following stimulation. There was a 50-fold greater increase in serum CK in CXMD compared with normal dogs following exercise. These results indicate greater muscle injury in CXMD muscle, and suggest that in the absence of dystrophin, exercise-induced muscle injury may play a role in the dystrophic process.
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PMID:Canine X-linked muscular dystrophy studied with in vivo phosphorus magnetic resonance spectroscopy. 174 83

Animal models have proven very useful in furthering insight into a number of muscle diseases. Studies of ethanol-fed rats are being used to understand the pathogenetic mechanisms underlying acute and chronic myopathy induced by ethanol. Several animal species, including mice, dogs, and cats, develop X-linked muscular dystrophies, which have genetic defects identical to those of Duchenne muscular dystrophy. As in the human disease, these animals lack dystrophin. They are being used to investigate the mechanisms by which lack of dystrophin results in weakness and to examine myoblast transfer as a treatment modality. A model of eosinophilia-myalgia syndrome has recently been induced in Lewis rats by the feeding of L-tryptophan samples that were implicated in the clinical syndrome in humans, making possible studies of the pathogenesis of this interesting new entity. A dermatomyositis-like syndrome occurs spontaneously in dogs, and polymyositis-like illnesses can be induced in mice by immunization with muscle or following infection with selected viruses, especially enteroviruses. Study of the latter is helping us understand mechanisms in the etiology and pathogenesis of inflammatory myositis and virus-induced autoimmunity.
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PMID:Animal models of myopathy. 177 47

We studied a 29-year-old man with slowly progressive proximal leg weakness, calf hypertrophy, and high serum levels of creatine kinase activity. Clinically, it was not possible to identify his as a sporadic instance of Becker muscular dystrophy (BMD) or one of spinal muscular atrophy. The problem arose because electromyography and elevated creatine kinase suggested a myopathy whereas changes in the muscle biopsy resembled a neurogenic disorder. The diagnosis of BMD was made by DNA analysis which detected a deletion at Xp21 and by immunoelectrophoresis and immunohistochemical tests that identified an abnormal form of gene product, dystrophin. These studies were important for genetic counselling, identifying an X-linked disease instead of one that is autosomal recessive.
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PMID:Becker muscular dystrophy or spinal muscular atrophy?--Dystrophin studies resolve conflicting results of electromyography and muscle biopsy. 182 94


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