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)

A 15-year-old girl (case 1) was admitted to our hospital because of progressive muscle weakness of the lower limbs and numbness of the upper limbs. She noted these symptoms beginning at 13 years of age. Neurological examination revealed that deep tendon reflexes were absent and hypesthesia of touch and pain sensation were distributed in a glove-and-stocking pattern. Muscle weakness and atrophy were predominantly present in the distal portions of the extremities. There were obvious pes cavus and champagne-bottle shape deformities. The motor conduction velocity of the median nerve was markedly delayed and sensory potentials were not evoked in any nerves examined. Lumbar MRI showed thickening of the nerve radices. Cranial MRI showed thickening of the acoustic nerves, as well. Histological studies of a biopsied sural nerve revealed a marked decrease in the number of myelinated and unmyelinated fibers and remarkable onion bulb formation. The patient's clinical manifestations and histological findings were more severe than that seen in the usual case of CMT1A. Her mother (case 2, 39 years old) had similar neurological and electrophysiological findings. DNA duplication encoding peripheral myelin protein 22, was not detected in either case 1 or 2. Sequencing of DNA from these patients revealed the presence of a mutant allele containing an A- to G-substitution of nucleotide 245, which replaced tyrosine with cysteine in the extracellular Ig-domain of the P0 protein.
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PMID:[A familial Charcot-Marie-Tooth disease type 1B (CMTD1B) manifesting a new mutation of myelin P0 gene]. 753 89

We studied a family with nine of twenty members affected with Charcot-Marie-Tooth disease type 1A (CMT1A). The proband and her four affected sibs showed no duplication of the 17p11.2-p12 (CMT region). Two of the proband's affected daughters and three affected grandchildren showed duplication of the PMP-22 gene and of the marker VAW409R3 but not of the markers VAW412R3 and EW401. Pulsed field gel electrophoresis (PFGE) revealed a 220 kb SacII fragment in one CMT1A patient with duplication instead of a 500 kb SacII fragment as previously reported (1, 3, 4, 6-9). Our findings suggest a smaller size of the duplication in this CMT1A family. The disease segregates with the same haplotype in both duplicated and nonduplicated CMT1A patients. The clinical phenotype showed more severe weakness with earlier onset and motor nerve conduction velocities were characterized by more significant slowing in the patients with duplication than in the patients who did not show duplication.
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PMID:Charcot-Marie-Tooth neuropathy type 1A with both duplication and non-duplication. 809 3

Three genetic loci for the Charcot-Marie-Tooth (CMT) syndromes with slow motor nerve conduction velocities (hereditary motor and sensory neuropathy: HMSN type I) have been mapped to chromosomes 1 (CMT1B), 17 (CMT1A), and the X chromosome (CMTX). The clinical features of these three CMT subgroups are similar. To determine whether any clinical features distinguish CMTX families, the range of clinical findings and motor nerve conduction velocities were examined in two large CMTX families, the range of clinical findings and motor nerve conduction velocities were examined in two large CMTX families with CMTX proven by linkage to X-chromosome markers. CMTX males had more wasting and weakness than CMTX females or individuals with CMT1A. Patellar reflexes were more often retained in CMTX. Motor nerve conduction velocities were faster than in CMT1A. Intermediate-range median nerve conduction velocities were present in CMTX females (45 +/- 9 m/sec; range, 26 to 61 m/sec). These velocities were significantly faster than those for CMT1A females (22 +/- 8 m/sec, p < 0.0001). Median nerve conduction velocities in CMTX males (31 +/- 6 m/sec) were significantly slower than in CMTX females and faster than in CMT1A males (20 +/- 6 m/sec, p < 0.0001). The combination of slow conduction velocities in affected males (< 40 m/sec) and intermediate-range median motor conduction velocity results (> 40 m/sec) in affected or obligate carrier females is a useful distinguishing feature to separate CMTX from CMT1A, as intermediate conduction velocities are not present in autosomal-dominant dominant CMT1A families. This feature defines possible CMTX families for linkage studies. Families with no male-to-male inheritance of the syndrome, slow motor nerve conductions in affected males, and normal or intermediate-range conduction velocities in carrier females should be considered to be X-linked CMT families.
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PMID:Intermediate nerve conduction velocities define X-linked Charcot-Marie-Tooth neuropathy families. 825 57

This study presents a longitudinal comparison of motor nerve conduction velocities (MCVs) in patients with Charcot-Marie-Tooth type 1A with proven duplication of a segment of chromosome 17p11.2p12. Results were compared for 8 CMT1A duplication patients from one family whose MCV measurements were taken 22 years apart (1967 and 1989). Measurements from a total of seven median motor and five peroneal motor MCVs were compared. Median MCVs showed a slight reduction that averaged 2.2 m/s, and peroneal MCVs showed an average decrease of 3.0 m/s. In addition, mild objective increase in limb weakness was seen in only 1 of 8 patients and subjective symptoms of gradual worsening of leg strength were noted in half the patients over the same period. In this study of a small group of CMT1A patients with proven segmental duplication of chromosome 17p11.2p12, the motor conduction velocities and clinical motor exam did not change significantly over 22 years.
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PMID:Longitudinal studies of the duplication form of Charcot-Marie-Tooth polyneuropathy. 853 73

We describe 10 patients from a large family with early onset motor and sensory neuropathy. Six were still living at the time of the study. In all cases, early motor milestones had been achieved. Mean age at onset of symptoms was 34 months; these included progressive distal and proximal muscle weakness of lower limbs. Pes equinovarus developed in all patients during childhood. Slight facial weakness was present in four patients, and one of them also had bilateral facial synkinesia. Intellectual function was normal in all cases. There was no evidence of thickened peripheral nerves. All three adult patients (mean age, 27 years) were seriously handicapped and wheelchair-bound. Death occurred in the fourth to fifth decade of life and the duration of the illness varied from 27 to 39 years. Motor nerve conduction velocities ranged from 15 to 17 m/sec in the upper limbs of the youngest patients, and were undetectable in the adult patients. Sensitive action potentials were almost always absent. In all patients, auditory evoked potentials showed abnormally delayed interpeak I-III latencies. The most prominent pathologic finding was a highly unusual myelin abnormality consisting of irregular redundant loops and folding of the myelin sheath. The genealogic study gave strong evidence of autosomal-recessive inheritance. The molecular analysis failed to demonstrate either duplication in the chromosome 17p11.2-12, point mutations in the four exons of the PMP-22 (17p11.2) and the six exons of the Po (1q21-q25) genes, or linkage to chromosome 8q13-21.1.
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PMID:Autosomal recessive hereditary motor and sensory neuropathy with focally folded myelin sheaths: clinical, electrophysiologic, and genetic aspects of a large family. 862 74

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy in humans and has been associated with a partial duplication of chromosome 17 (CMT type 1A). We have generated a transgenic rat model of this disease and provide experimental evidence that CMT1A is caused by increased expression of the gene for peripheral myelin protein-22 (PMP22, gas-3). PMP22-transgenic rats develop gait abnormalities caused by a peripheral hypomyelination, Schwann cell hypertrophy (onion bulb formation), and muscle weakness. Reduced nerve conduction velocities closely resemble recordings in human patients with CMT1A. When bred to homozygosity, transgenic animals completely fail to elaborate myelin. We anticipate that the CMT rat model will facilitate the identification of a cellular disease mechanism and serve in the evaluation of potential treatment strategies.
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PMID:A transgenic rat model of Charcot-Marie-Tooth disease. 863 Feb 43

A 16-year-old school boy suffered from an insidious foot deformity. Slight degrees of symmetrical muscular weakness of the distal lower limb muscles were observed. In addition, slight degrees of atrophy of the anterior tibial muscles with moderate degrees of pes cavus deformity and flexion contracture of the toes of both feet were observed. In the upper and lower limbs muscle stretch reflexes were decreased and absent, respectively. Vibratory and touch sensations were moderately and slightly decreased, respectively, in the toes. The median and ulnar motor conduction velocities (m/sec) were 21.1 and 13.2, respectively, with markedly prolonged distal latencies. The median and ulnar sensory conduction velocities (m/sec) were 21.5 and 10.1, respectively. No M-waves were recorded by stimulation of the tibial and peroneal nerves. Also no nerve action potential was elicited by stimulation of the sural nerve. A fascicular biopsy of the sural nerve was performed. The myelinated fibers showing segmental de- and re-myelination were frequently found in teased fiber preparations. The density of myelinated fibers was markedly decreased, and both demyelinated axons and onion-bulbs were also observed by light and electron microscopy in the Epon-embedded sections. Based on the neurological examination and nerve conduction studies, although other family members were not examined, a diagnosis of HMSN type I was made. To clarify the genetic abnormality, a systematic study of the genomic DNA was made. A DNA duplication in the chromosome 17p11.2-12 was not observed. The single-strand conformational polymorphism method showed an abnormal extra band in the exon 3 encoding peripheral myelin protein (PMP)-22 gene of the patient compared with the control. The direct sequencing analysis of the exon 3 revealed a guanine to cytosine substitution that caused a substitution of arginine for glycine at amino acid position 93 of PMP-22. The digestion of the exon 3 with Sty I showed the presence of a mutant and normal allele of the PMP-22 gene indicating autosomal dominant heredity. This type of PMP-22 gene mutation is different from any type of PMP-22 mutations reported in the literature. The mutation is located in the intracellular domain of PMP-22. The mechanism by which the mutation induce demyelination of the peripheral myelin remains to be elucidated. Reports of patients with a point mutation of amino acids of PMP-22 are rare in the literature. This is the first Japanese patient with a new type of mutation of the PMP-22 gene.
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PMID:[A case of hereditary motor and sensory neuropathy type I with a new type of peripheral myelin protein (PMP)-22 mutation]. 877 4

We studied phenotypic heterogeneity in 18 Japanese patients with Charcot-Marie-Tooth disease type 1A (CMT1A) with PMP-22 gene duplication, together with heterogeneity of duplication size. In order to detect the duplication of PMP-22 gene region, the PMP-22 cDNA and a polymorphic marker VAW409R3 were used as probes for Southern blot analysis. As the clinical phenotypes, we assessed the degree of foot deformity, muscular weakness and atrophy, tendon reflexes, sensory impairment and electrophysiologic and sural nerve biopsy findings. Although the degree of muscular weakness and atrophy was slightly more severe in the advanced age, there was a patient with calf hypertrophy in the older age or a patient with marked muscular atrophy of the leg in the younger age. The incidence of foot deformities and sensory impairment was high and these phenotypes did not relate to aging. Diminished or absent tendon reflexes and slowing of motor conduction velocities were commonly seen, but the motor conduction velocity varied greatly among the patients. The clinical phenotypes were extensively variable among the CMT 1A patients with the same gene mutation of PMP-22 gene duplication, suggesting that there is a factor other than PMP-22 gene duplication, which influences phenotypic manifestation in CMT 1A.
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PMID:[Phenotypic heterogeneity in Japanese Charcot-Marie-Tooth disease type 1A patients with PMP-22 gene duplication]. 882 90

Hereditary neuropathy with liability to pressure palsies is caused by deletion of the PMP-22 gene. As its relatively mild symptoms may escape detection by clinical examination alone, we screened the gene in patients with multiple entrapment neuropathy (MEN) that had been diagnosed by nerve conduction studies (NCS). Two of the eight patients with MEN had deletion of the gene. The characteristic features that distinguished them from the other MEN patients were predominantly sensory deficits associated with mild weakness and subclinical polyneuropathy as detected by NCS.
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PMID:Hereditary neuropathy with liability to pressure palsies: distinguishing clinical and electrophysiological features among patients with multiple entrapment neuropathy. 885 51

Clinical, electrophysiological and genetic linkage studies were performed on a large autosomal dominant family with Charcot-Marie-Tooth axonal neuropathy type 2 (CMT2) with 38 members of which 14 were affected. Onset of the disease was between 16 and 30 years of age with weakness and atrophy of the hands more severe than of the feet with slow progressive course in 12 patients. Deep tendon reflexes were absent in the upper extremities and decreased in the lower extremities. There was distal hypesthesia for touch, proprioception and vibration sense for the hands more than for the feet. Motor nerve conduction velocities showed normal values (48-53 M/s) with normal latencies (2-3 msec) and electromyography revealed signs of denervation. Genetic linkage analysis used 167 short tandem repeat markers (STRPs) spaced throughout the 22 autosomes. Linkage to the short arm of chromosome 7 at 7p14 was found using the marker D7S435 (Z = 4.83 at theta = 0). Flanking markers were D7S1808 and D7S1806 and the genetic distance between them was 6.8 cM. The multipoint linkage analysis gave a peek multipoint lod score of 6.89 between the markers D7S1808 and D7S435. Linkage analysis showed significantly negative lod scores (with values less than -2) with markers of chromosomes 1 and 3 where CMT axonal forms have been previously mapped. PFGE analysis indicated the absence of the CMT1A duplication. Our findings are consistent with a new genetic type of axonal CMT neuropathy designated by us as CMT2D. Potential candidate genes are multiple T-cell gamma receptor genes which map to the same cytogenetic interval as CMT2D neuropathy.
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PMID:Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D). 887 80


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