Longitudinal studies of the duplication form of Charcot‐Marie‐Tooth polyneuropathy

Killian, James M.; Tiwari, Pinky S.; Jacobson, Sheila; Jackson, Robert D.; Lupski, James R.

doi:10.1002/(sici)1097-4598(199601)19:1<74::aid-mus10>3.3.co;2-2

Cited by 10 publications

(11 citation statements)

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“…Because myelination proceeds in humans from 5 months of gestation until the age of about 14 years, 15 this period is presumably the most vulnerable window to PMP22 duplication. Such a pathological evolution agrees with the electrophysiological findings in the present series and in other crosssectional 3,14 and longitudinal studies 16 ; progressing age worsens neither the MNCV slowing nor the decreased compound motor action potential ampli- tudes. Whereas the electrophysiological measures in the duplicated form of CMT1A do not progress with age, the clinical deficits apparently do.…”

Section: Discussionsupporting

confidence: 93%

Clinical and pathological correlations in charcot-marie-tooth neuropathy type 1A with the 17p11.2p12 duplication: A cross-sectional morphometric and immunohistochemical study in twenty cases

et al. 1998

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In a cross‐sectional, clinical, and morphometric analysis we assessed the correlation between the clinical and pathological evolution of disease in 20 unrelated patients of various ages affected by Charcot–Marie–Tooth neuropathy type 1A (CMT1A) with the 17p11.2p12 (peripheral myelin protein 22, PMP22) duplication. The severity of neurologic deficits and slowing of motor conduction velocity at the median nerve did not vary significantly with the patients' age. The amount of demyelination was significantly higher below 15 years than in older age groups; in contrast, myelinated fiber and onion bulb densities were similar at all ages. The results indicate that in duplicated CMT1A, the pathological process develops early in life and progresses little during the course of the disease. Younger patients had lower g‐ratio values, suggesting that the trigger of demyelination in early years could be a hypermyelination, resulting from PMP22 overexpression. Yet none of the 20 patients examined had immunohistochemical evidence of altered PMP22 expression. The early onset and development of the disorder make it difficult to detect PMP22 overdosage in nerve biopsies. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:869–877, 1998.

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Section: Discussionsupporting

confidence: 93%

Clinical and pathological correlations in charcot-marie-tooth neuropathy type 1A with the 17p11.2p12 duplication: A cross-sectional morphometric and immunohistochemical study in twenty cases

et al. 1998

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“…It is of interest that, although these findings have already been noted in previous reports [2,11], the current notion is that NCV does not change significantly through the life of CMT1A patients [7][8][9]. Birouk and colleagues found in their large sample of CMT1A patients that NCV increased with age and they interpreted the more evident lower NCV in younger patients as an expression of early diagnosis in younger CMT1A patients due to their more severe symptoms [2].…”

Section: Discussionmentioning

confidence: 70%

“…In CMT1A, MNCV is uniformly reduced in all nerves and values <38 m/s are highly diagnostic [2,3]. This electrophysiological hallmark, fully penetrant since the first years of life [4][5][6], remains fairly stable through life [7][8][9] and does not correlate with disability, whereas compound motor action potential (CMAP) amplitude that is a surrogate marker of axonal degeneration does [3].…”

Section: Introductionmentioning

confidence: 99%

Nerve conduction velocity in CMT1A: what else can we tell?

Manganelli

Pisciotta

Reilly

et al. 2016

Euro J of Neurology

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Background and purpose Charcot-Marie-Tooth disease (CMT) type 1A is characterized by uniformly reduced nerve conduction velocity (NCV) that is fully penetrant since the first years of life, remains fairly stable through the life and does not correlate with disability whereas compound muscular action potential (CMAP) amplitude does. The aim of the present study was to analyze the large amount of electrophysiological data collected in the ascorbic acid trial in Italy and the UK (CMT-TRIAAL/CMT-TRAUK) and to use these data to gain insights into the pathophysiology of NCV in CMT1A. Methods Baseline electrophysiological data from 271 patients were analysed. Electrophysiological recordings were taken from the motor ulnar, median and peroneal nerves and the sensory ulnar nerve. Distal motor latency (DML), motor (MNCV) and sensory (SNCV) nerve conduction velocity, and amplitudes of CMAPs and sensory action potentials were assessed. Electrophysiological findings were correlated with age of patients at examination and the Charcot–Marie–Tooth Examination Score (CMTES). Results NCV was markedly and uniformly reduced. CMAP amplitudes were overall reduced but more severely in lower limbs. DML decreased and MNCV and SNCV increased with age of the patients, whereas CMAP amplitudes worsened with age and also correlated with CMTES. Conclusions This is the largest sample of electrophysiological data obtained so far from CMT1A patients. Axonal degeneration as assessed by means of CMAP amplitude reflected clinical impairment and was consistent with a slowly progressive length-dependent neuropathy. All patients typically had markedly slowed NCV that did, however, slightly increase with age of the patients. The improvement of NCV might depend on myelin thickness remodelling that occurs during the adult life of CMT1A patients.

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“…Findings from a number of recent clinical and experimental studies (Killian et al 1996;Garcia et al 1998;Robertson et al 1999;Sahenk 1999;Sancho et al 1999) of the common autosomal dominant demyelinating forms of Charcot-Marie-Tooth (CMT) disease have indicated that the neurological deficit in demyelinating neuropathies is related to axonal loss, rather than to demyelination per se. The neuropathologic features of HMSNL make it impossible to attribute the primary defect to either Schwann cells or neurons, and they strongly suggest that impairment of Schwann cell-axonal interaction is a major component of the pathogenesis of this disease.…”

Section: Introductionmentioning

confidence: 99%

N‐MYC Downstream‐Regulated Gene 1 Is Mutated In Hereditary Motor And Sensory Neuropathy‐LOM

Kalaydjieva¹,

Gresham²,

Gooding³

et al. 2001

J Peripheral Nervous Sys

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Citation for published version (APA):Kalaydjieva, L., Gresham, D., Gooding, R., Heather, L., Baas, F., de Jonge, R., ... Thomas, P. K. (2000). N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom. American Journal of Human Genetics, 67, 47-58. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Download date: 11 May 2018Am. J. Hum. Genet. 67:47-58, 2000 47 Hereditary motor and sensory neuropathies, to which Charcot-Marie-Tooth (CMT) disease belongs, are a common cause of disability in adulthood. Growing awareness that axonal loss, rather than demyelination per se, is responsible for the neurological deficit in demyelinating CMT disease has focused research on the mechanisms of early development, cell differentiation, and cell-cell interactions in the peripheral nervous system. Autosomal recessive peripheral neuropathies are relatively rare but are clinically more severe than autosomal dominant forms of CMT, and understanding their molecular basis may provide a new perspective on these mechanisms. Here we report the identification of the gene responsible for hereditary motor and sensory neuropathy-Lom (HMSNL). HMSNL shows features of Schwann-cell dysfunction and a concomitant early axonal involvement, suggesting that impaired axonglia interactions play a major role in its pathogenesis. The gene was previously mapped to 8q24.3, where conserved disease haplotypes suggested genetic homogeneity and a single founder mutation. We have reduced the HMSNL interval to 200 kb and have characterized it by means of large-scale genomic sequencing. Sequence analysis of two genes located in the critical region identified the founder HMSNL mutation: a premature-termination codon at position 148 of the N-myc downstream-regulated gene 1 (NDRG1). NDRG1 is ubiquitously expressed and has been proposed to play a role in growth arrest and cell differentiation, possibly as a signaling protein shuttling between the cytoplasm and the nucleus. We have studied expression in peripheral nerve and have detected particularly high levels in the Schwann cell. Taken together, these findings point to NDRG1 having a role in the peripheral nervous system, possibly in the Schwann-cell signaling necessary for axonal survival. N-myc Downstream-Regulated Gene 1 Is Muta...

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Longitudinal studies of the duplication form of Charcot‐Marie‐Tooth polyneuropathy

Cited by 10 publications

References 0 publications

Clinical and pathological correlations in charcot-marie-tooth neuropathy type 1A with the 17p11.2p12 duplication: A cross-sectional morphometric and immunohistochemical study in twenty cases

Clinical and pathological correlations in charcot-marie-tooth neuropathy type 1A with the 17p11.2p12 duplication: A cross-sectional morphometric and immunohistochemical study in twenty cases

Nerve conduction velocity in CMT1A: what else can we tell?

N‐MYC Downstream‐Regulated Gene 1 Is Mutated In Hereditary Motor And Sensory Neuropathy‐LOM

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