The PMP22 Gene and Its Related Diseases

Li, Jun; Parker, Brett; Martyn, Colin; Natarajan, Chandramohan; Guo, Jiasong

doi:10.1007/s12035-012-8370-x

Cited by 216 publications

(284 citation statements)

References 222 publications

(324 reference statements)

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“…30 In addition, although the exact role of PMP22 is still under investigation, it has been observed that PMP22 overexpression may affect Schwann cell proliferation, differentiation, and death. 31 The correlation of ENF loss with both MC density and tactile thresholds suggests that small fiber and large fiber degeneration in CMT1A follow a parallel course.…”

Section: Statistical Analysis We Used Student T Test For Unpaired Datamentioning

confidence: 96%

Small nerve fiber involvement in CMT1A

et al. 2015

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Objective: To assess the involvement of small nerve fibers in Charcot-Marie-Tooth type 1A (CMT1A). Methods:We used indirect immunofluorescence and confocal microscopy on punch biopsies from glabrous (fingertip) and hairy (thigh and leg) skin of 20 unrelated patients with CMT1A to quantify somatic and autonomic nerve fibers. In particular, we quantified epidermal nerve fibers (ENF), Meissner corpuscles (MC), intrapapillary myelinated endings (IME), and sudomotor nerves. We correlated morphologic data with findings from quantitative sensory testing, sudomotor output, sympathetic skin response, and cardiovascular reflexes. A control population of healthy ageand sex-matched controls was included with a matching ratio of 1:2.Results: We found a length-dependent loss of ENFs that worsened with aging. We also observed a loss of MCs, IMEs, and sudomotor nerves. The loss of ENF at distal leg correlated with the increase in heat-pain thresholds (p , 0.05) and with tactile thresholds (p , 0.05). Sudomotor nerve fiber loss correlated with ENF density (p , 0.05) and sweating output (p , 0.001). Conclusions:We demonstrated through morphologic, physical, and psychophysical testing that small somatic and autonomic fibers are abnormal and cause symptoms in patients with CMT1A. Awareness of such symptoms by the clinician could lead to better treatment. Neurology ® 2015;84:407-414 GLOSSARY ANS 5 autonomic nervous system; CGRP 5 calcitonin gene-related peptide; CMT 5 Charcot-Marie-Tooth; CMT1A 5 Charcot-Marie-Tooth type 1A; CMTNS 5 Charcot-Marie-Tooth neuropathy score; Col IV 5 collagen IV; CVR 5 cardiovascular reflexes; DST 5 dynamic sweat test; ENF 5 epidermal nerve fibers; IME 5 intrapapillary myelinated endings; LEP 5 laser-evoked potentials; MC 5 Meissner corpuscles; PGP 5 protein gene product; PMP22 5 peripheral myelin protein 22 kD; QST 5 quantitative sensory testing; SFN-SIQ 5 Small Fiber Neuropathy Symptoms Inventory Questionnaire; SSR 5 sympathetic skin response; SubP 5 substance P; VIP 5 vasoactive intestinal peptide.Charcot-Marie-Tooth (CMT) diseases are a heterogeneous group of inherited motor and sensory neuropathies with a general prevalence of 1:2,500.

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Section: Statistical Analysis We Used Student T Test For Unpaired Datamentioning

confidence: 96%

Small nerve fiber involvement in CMT1A

et al. 2015

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“…The PMP22 protein is best known for its structural role in the peripheral nervous system [Li et al, 2013]. However, a role in tumorigenesis might be concluded from the reported overexpression of PMP22 in osteosarcomas and other tumor tissues [Huhne et al, 1999;Evtimova et al, 2003;Li et al, 2005;Both et al, 2012].…”

Section: Cops3 Pmp22mentioning

confidence: 99%

Oncogenic Properties of Candidate Oncogenes in Chromosome Region 17p11.2p12 in Human Osteosarcoma

Both

Asbroek

et al. 2016

Cytogenet Genome Res

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Osteosarcomas are primary tumors of bone that most often develop in adolescents. They are characterized by complex genomic changes including amplifications, deletions, and translocations. The chromosome region 17p11.2p12 is frequently amplified in human high grade osteosarcomas (25% of cases), suggesting the presence of one or more oncogenes. In previous studies, we identified 9 candidate oncogenes in this region (GID4, ARGHAP44, LRRC75A-AS1, TOP3A, COPS3, SHMT1, PRPSAP2, PMP22, and RASD1). The aim of the present study was to determine their oncogenic properties. Therefore, we generated osteosarcoma cell lines overexpressing these genes, except for LRRC75A-AS1 and PRPSAP2, and subjected these to functional oncogenic assays. We found that TOP3A, SHMT1, and RASD1 overexpression provided increased proliferation and that ARGHAP44, COPS3, and PMP22 overexpression had a stimulatory effect on migration and invasion of the cells. COPS3 and PMP22 overexpression additionally improved the ability of the cells to form new colonies. No oncogenic effect could be demonstrated for GID4 overexpression. We conclude that the concerted amplification-mediated overexpression of these genes in 17p11.2p12 may contribute to the oncogenic process in malignant osteosarcoma.

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“…Analogous analyses were performed for the inter-rater data. 30 were also studied. Patients with HNPP reported transient, asymmetric, focal sensory loss and weakness following mechanical stresses; conduction velocities (37.7 6 3.5 m/s) were between the values observed in CMT1A and control cohorts.…”

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confidence: 99%

Proximal nerve magnetization transfer MRI relates to disability in Charcot-Marie-Tooth diseases

et al. 2014

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Objective: The objectives of this study were (1) to develop a novel magnetization transfer ratio (MTR) MRI assay of the proximal sciatic nerve (SN), which is inaccessible via current tools for assessing peripheral nerves, and (2) to evaluate the resulting MTR values as a potential biomarker of myelin content changes in patients with Charcot-Marie-Tooth (CMT) diseases.Methods: MTR was measured in the SN of patients with CMT type 1A (CMT1A, n 5 10), CMT type 2A (CMT2A, n 5 3), hereditary neuropathy with liability to pressure palsies (n 5 3), and healthy controls (n 5 21). Additional patients without a genetically confirmed subtype (n 5 4), but whose family histories and electrophysiologic tests were consistent with CMT, were also included. The relationship between MTR and clinical neuropathy scores was assessed, and the interscan and inter-rater reliability of MTR was estimated.Results: Mean volumetric MTR values were significantly decreased in the SN of patients with CMT1A (33.8 6 3.3 percent units) and CMT2A (31.5 6 1.9 percent units) relative to controls (37.2 6 2.3 percent units). A significant relationship between MTR and disability scores was also detected (p 5 0.01 for genetically confirmed patients only, p 5 0.04 for all patients). From interscan and inter-rater reliability analyses, proximal nerve MTR values were repeatable at the slicewise and mean volumetric levels. Charcot-Marie-Tooth (CMT) diseases are a group of inherited neuropathies that affect motor and sensory nerves. A majority of CMT phenotypes can be classified as primary demyelination/dysmyelinating (CMT1) or primary axonal (CMT2) neuropathies.1,2 CMT type 1A (CMT1A z 80% of CMT1 cases 3,4 ) arises from duplication of the peripheral myelin protein 22 (PMP22) gene 5,6 and results in dysmyelination and secondary axonal loss. 7 CMT type 2A (CMT2A z 35% of CMT2 cases 8 ) is caused by missense mutations in the gene that encodes for mitofusin 2 9 and leads to primary axonal degeneration. 8 Although the pathologic features of CMT1A/CMT2A are different, length-dependent axonal loss occurs in both and is predictive of outcomes.

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The PMP22 Gene and Its Related Diseases

Cited by 216 publications

References 222 publications

Small nerve fiber involvement in CMT1A

Small nerve fiber involvement in CMT1A

Oncogenic Properties of Candidate Oncogenes in Chromosome Region 17p11.2p12 in Human Osteosarcoma

Proximal nerve magnetization transfer MRI relates to disability in Charcot-Marie-Tooth diseases

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