Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0700208 (scoliosis)
 8,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The most frequent type of Charcot-Marie-Tooth (CMT) neuropathy is that associated with the 17p11.2-p12 chromosome duplication, whose characteristics have been well described in European and North American populations. In this study, we analyzed a Brazilian population exhibiting the mutation, found in 57 patients from 42 families (79%) of a cohort of 53 families with demyelinating CMT. Almost 20% of the duplicated cases were sporadic. In 77% of the duplicated families the mutation event occurred in the hot spot area of the CMT1A-Rep region. Forty-five percent of patients were females, 84% were Caucasians and 13% of African descent. Distal limb weakness was the most frequent abnormality, appearing in 84% of patients, although uncommon manifestations such as severe proximal weakness, floppy baby syndrome, diaphragmatic weakness and severe scoliosis were also observed. One patient was wheelchair-bound, and three suffered severe hand weakness. Sensory abnormalities were detected in 84% of the cases, but 80% were unaware of this impairment. Twelve patients complained of positive sensory manifestations such as pain and paresthesias. Progression was reported by 40%. Motor conduction velocities in the upper limbs were always less than 35 m/s, and less than 30.4 m/s in the peroneal nerve. The findings of this study expand the clinical spectrum of the disease.
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PMID:17p duplicated Charcot-Marie-Tooth 1A: characteristics of a new population. 1576 65

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous group of disorders sharing the same clinical phenotype, characterized by distal limb muscle wasting and weakness, usually with skeletal deformities, distal sensory loss, and abnormalities of deep tendon reflexes. Mutations of genes involved in different functions eventually lead to a length-dependent axonal degeneration, which is the likely basis of the distal predominance of the CMT phenotype. Nerve conduction studies are important for classification, diagnosis, and understanding of pathophysiology. The subdivision into demyelinating CMT1 and axonal CMT2 types was a milestone and is still valid for the majority of patients. However, exceptions to this partition are increasing. Intermediate conduction velocities are often found in males with X-linked CMT (CMTX), and different intermediate CMT types have been identified. Moreover, for some genes, different mutations may result either in demyelinating CMT with slow conduction, or in axonal CMT. Nerve conduction slowing is uniform and diffuse in the most common CMT1A associated with the 17p12 duplication, whereas it is often asymmetric and nonhomogeneous in CMTX, sometimes rendering difficult the differential diagnosis with acquired inflammatory neuropathies. The demyelinating recessive forms, termed CMT4, usually have early onset and run a more severe course than the dominant types. Pure motor CMT types are now classified as distal hereditary motor neuronopathy. The diagnostic approach to the identification of the CMT subtype is complex and cannot be based on the clinical phenotype alone, as different forms are often clinically indistinguishable. However, there are features that may be of help in addressing molecular investigation in a single patient. Late onset, prominent or peculiar sensory manifestations, autonomic nervous system dysfunction, cranial nerve involvement, upper limb predominance, subclinical central nervous system abnormalities, severe scoliosis, early-onset glaucoma, neutropenia are findings helpful for diagnosis.
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PMID:Clinical and electrophysiological aspects of Charcot-Marie-Tooth disease. 1677 64

We report monozygotic twins, who presented with a clinical picture of Charcot-Marie-Tooth disease type 1 (CMT1) with bilateral foot drop, pes cavus, thoracic kyphosis, and scoliosis. Hereditary neuropathy with liability to pressure palsies (HNPP) showed up in one of them. Neurography showed demyelinating neuropathy, typical for CMT1, and transient conduction block in the ulnar nerve correlating with clinical ulnar palsy due to minor mechanical stress in only one of them. Genetic analysis revealed novel small de novo deletion c.407_418del12 in the PMP22 gene. Our patient shows the rarely reported combination of CMT1A and HNPP, caused by an in-frame deletion in the PMP22 gene. HNPP is in the majority of cases correlated with heterozygous deletion of the whole PMP22 gene or other mutations leading to functional haploinsufficiency. The cases give further evidence that pathogenesis of HNPP is not completely understood and can obviously result from existence of a defective protein, too. The intrafamiliar phenotypic variability, even in monozygotic twins, confirms the well-known fact that factors apart from genetics contribute to the clinical course.
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PMID:Overlap phenotype between CMT1A and hereditary neuropathy with liability to pressure palsies caused by the novel small in-frame deletion c.407_418del12 in PMP22 gene. 2526 22