Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

A man was identified with two X-chromosomal neuromuscular disorders, X-linked Charcot-Marie-Tooth disease (CMTX) and Becker muscular dystrophy (BMD). The neuropathy could be tracked in the family and was found to be caused by a mutation in the connexin32 gene on Xq13. 1. The muscular dystrophy was sporadic owing to a de novo deletion in the dystrophin gene located in band Xp21.2. Although these genetic alterations of the same X-chromosome are considered as physically independent, their combination resulted in a unique phenotype with severe wasting of proximal as well as distal muscles and rapid progression of both conditions.
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PMID:Becker muscular dystrophy combined with X-linked Charcot-Marie-Tooth neuropathy. 1079 9

Charcot-Marie-Tooth disease (CMT) is characterized by distal muscle weakness and wasting, often resulting in foot deformities and gait disturbances, distal sensory impairment and by more or less typical changes in sural nerve biopsy. CMT type 1 is also characterized by reduced nerve conduction velocities. For these demyelinating subtypes, most frequently a 1.5 Mb tandem duplication in chromosome 17p11.2-12 comprising the gene for the peripheral myelin protein 22 (PMP22) is observed (CMT1A), but point mutations in PMP22 have also rarely been reported. X-linked, dominant CMTX1 disease is the second most common type of these hereditary motor and sensory neuropathies (HMSN). Mutations in the X chromosomal gene Connexin32 (Cx32) synonymous gap junction beta-1 (GJB1) are detectable in most X-linked CMT families. We report a novel missense mutation--Tyr65His--in the first extracelullar domain of the Cx32 gene in a Czech CMTX1 family. The mutation was not detectable in 50 healthy controls. The clinical phenotype in both the male proband and his mother was moderate with pronounced peroneal weakness and foot drop. Nerve conduction velocities were intermediately decreased (31-38 m/s) in both patients and slowing of central acoustic conduction (BAEP) was found in both the son and the mother whereas visual central conduction slowing (VEP) was detectable only in the son.
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PMID:Charcot-Marie-Tooth type X: A novel mutation in the Cx32 gene with central conduction slowing. 1156 88

Charcot-Marie-Tooth disease is a clinically and genetically heterogeneous group of inherited neuropathies. The common clinical symptoms include distal muscle weakness, wasting and impaired distal sensation, more in the legs than in the arms, and reduced or absent reflexes. Moreover, foot and hand deformities are often encountered. A distinction between a primarily demyelinating or axonal neuropathy is often possible by means of nerve conduction studies. The major groups of inheritance are the autosomal dominant CMT1 (demyelinating), CMT2 (axonal) and the X-linked type (CMTX), but there are also autosomal recessive demyelinating (CMT4) and axonal (AR-CMT2) forms. The number of genes and loci is steadily increasing, with genes encoding proteins involved in myelin maintenance and axonal function, but also with genes encoding proteins, the function of which in peripheral nerve maintenance is notyet clear. Despite the increase in the number of known genes, especially for CMT2, there are many patients in whom no mutation can yet be found.
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PMID:[From gene to disease; Charcot-Marie-Tooth disease or the hereditary motor and sensory neuropathies]. 1603 95

Charcot-Marie-Tooth (CMT) disease, also known as peroneal muscular atrophy or hereditary motor and sensory neuropathy, is among the most frequent hereditary disorders of the nervous system. The relatively homogeneous clinical phenotype involves mainly progressive weakness and wasting of distal muscles; it starts and predominates in the peroneal muscles. Electrophysiological and pathology data distinguish two principal forms of CMT: demyelinating and axonal. More than 20 distinct genetic subtypes have been identified to date and other new loci and genes remain to be discovered, thus demonstrating wide genetic heterogeneity and a number of different pathophysiological mechanisms. The classification of these different forms is based on both the mode of inheritance--autosomal dominant, recessive or X-linked--and the neuropathy type--demyelinating or axonal or "intermediate". The principal dominant forms are CMT1A, due to a duplication or point mutation in the PMP22 gene, and CMTX, due to mutations in the connexin 32 gene. Autosomal recessive forms are more frequent in North Africa. The most common involve mutations of GDAP1 or lamin A/C and generally lead to more severe phenotypes than the dominant forms. The great genetic heterogeneity necessitates a strategy for genetic diagnosis. It is based in part on the classification of the different genetic forms and in part on the phenotypic particularities and the frequency of the responsible genes in the population under study.
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PMID:[Charcot-Marie-Tooth disease]. 1913 35