X-linked Charcot-Marie-Tooth disease with connexin 32 mutations

Birouk, N.; LeGuern, Eric; Maisonobe, Thierry; Rouger, H.; Gouider, Riadh; Tardieu, S; Gugenheim, Michel; Routon, M. C.; Léger, Juliane; Agid, Yves; Brice, Alexis; Bouché, P

doi:10.1212/wnl.50.4.1074

Cited by 166 publications

(155 citation statements)

References 13 publications

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“…Nerve conduction velocities are typically in 30 -40 m/s in affected males and 30 -50 m/s in affected females (Nicholson and Nash, 1993;Rouger et al, 1997;Birouk et al, 1998;Hahn et al, 1999;Senderek et al, 1999); this is faster than the 20 m/s typically seen in CMT1A patients . In addition, electrophysiological studies pronounced loss of distal motor axons in CMT1X (Rozear et al, 1987;Hahn et al, 1990Hahn et al, , 1999Nicholson and Nash, 1993;Rouger et al, 1997;Birouk et al, 1998;Senderek et al, 1999). Finally, nerve biopsies show more axonal loss and less remyelination than is typically seen in CMT1A or CMT1B (Sander et al, 1998;Hahn et al, 2001).…”

Section: Discussionmentioning

confidence: 82%

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Transgenic Expression of HumanConnexin32in Myelinating Schwann Cells Prevents Demyelination inConnexin32-Null Mice

Scherer¹,

Xu²,

Messing³

et al. 2005

J. Neurosci.

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Mutations in Gap Junction ␤1 (GJB1), the gene encoding the gap junction protein connexin32 (Cx32), cause the X-linked form of Charcot-Marie-Tooth disease (CMT1X), an inherited demyelinating neuropathy. We investigated the possibility that the expression of mutant Cx32 in other cells besides myelinating Schwann cells contributes to the development of demyelination. Human Cx32 was expressed in transgenic mice using a rat myelin protein zero (Mpz) promoter, which is exclusively expressed by myelinating Schwann cells. Male mice expressing the human transgene were crossed with female Gjb1/cx32-null mice; the resulting male offspring were all cx32-null (on the X chromosome), and one-half were transgene positive. In these transgenic mice, all of the Cx32 was derived from the expression of the transgene and was found in the sciatic nerve but not in the spinal cord or the liver. Furthermore, the Cx32 protein was properly localized (within incisures and paranodes) in myelinating Schwann cells. Finally, the expression of human Cx32 protein "rescued" the phenotype of cx32-null mice, because the transgenic mice have significantly fewer demyelinated or remyelinated axons than their nontransgenic littermates. These results indicate that the loss of Schwann-cell-autonomous expression of Cx32 is sufficient to account for demyelination in CMT1X.

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Section: Discussionmentioning

confidence: 82%

“…Finally, nerve biopsies show more axonal loss and less remyelination than is typically seen in CMT1A or CMT1B (Sander et al, 1998;Hahn et al, 2001). These data have lead to the frequent supposition that CMT1X is an axonal neuropathy (Hahn et al, 1990;Timmerman et al, 1996;Birouk et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Transgenic Expression of HumanConnexin32in Myelinating Schwann Cells Prevents Demyelination inConnexin32-Null Mice

Scherer¹,

Xu²,

Messing³

et al. 2005

J. Neurosci.

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“…Affected males with the CMT1X phenotype have moderate to severe symptoms, whereas heterozygous females are usually less affected with mild symptoms. The mMNCV typically ranges from 30 to 40 m/s in affected males with GJB1 mutation and 30-50 m/s in affected females with the CMT1X phenotype, which is faster than in patients with the demyelinating form and slower than in patients with the axonal form of CMT [11][12][13] .…”

Section: Inf2mentioning

confidence: 99%

Intermediate Charcot-Marie-Tooth disease

Liu

Zhang

2014

Neurosci. Bull.

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Charcot-Marie-Tooth (CMT) disease is a common neurogenetic disorder and its heterogeneity is a challenge for genetic diagnostics. The genetic diagnostic procedures for a CMT patient can be explored according to the electrophysiological criteria: very slow motor nerve conduction velocity (MNCV) (<15 m/s), slow MNCV (15-25 m/s), intermediate MNCV (25-45 m/s), and normal MNCV (>45 m/s). Based on the inheritance pattern, intermediate CMT can be divided into dominant (DI-CMT) and recessive types (RI-CMT). GJB1 is currently considered to be associated with X-linked DI-CMT, and MPZ, INF2, DNM2, YARS, GNB4, NEFL, and MFN2 are associated with autosomal DI-CMT. Moreover, GDAP1, KARS, and PLEKHG5 are associated with RI-CMT. Identifi cation of these genes is not only important for patients and families but also provides new information about pathogenesis. It is hoped that this review will lead to a better understanding of intermediate CMT and provide a detailed diagnostic procedure for intermediate CMT.

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“…Muscle strengths of flexor and extensor muscles were assessed manually using the standard medical research council (MRC) scale. In order to determine physical disability, we used two scales, a functional disability scale (FDS) (Birouk et al 1998) and a CMT neuropathy score (CMTNS) (Shy et al 2005). Disease severity was determined for each patient using a nine-point FDS that was based on the following criteria: 0, normal; 1, normal but with cramps and fatigability; 2, an inability to run; 3, walking difficulty but unaided; 4, walking with a cane; 5, walking with crutches; 6, walking with a walker; 7, wheelchair bound; and 8, bedridden.…”

Section: Clinical Assessmentsmentioning

confidence: 99%

“…Duplication is found in up to approximately 70% of patients with CMT1 (Szigeti et al 2006). Deletion of the same region by the unequal crossover is associated with hereditary neuropathy with liability to pressure palsies (HNPP, MIM# 162500) (Chance et al 1993;Mariman et al 1994). It is estimated that about 5Á24% of the duplication occur de novo (Hoogendijk et al 1992;Nelis et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Wide phenotypic variations in Charcot-Marie-Tooth 1A neuropathy with rare copy number variations on 17p12

Kanwal

Choi

Kim

et al. 2011

Animal Cells and Systems

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Charcot-Marie-Tooth disease (CMT) is clinically heterogeneous hereditary motor and sensory neuropathies with genetic heterogeneity, age-dependent penetrance, and variable expressivity. Rare copy number variations by nonrecurrent rearrangements have recently been suggested to be associated with Charcot-Marie-Tooth 1A (CMT1A) neuropathy. In our previous study, we found three Korean CMT1A families with rare copy number variations (CNVs) on 17p12 by nonrecurrent rearrangement. Careful clinical examinations were performed in all the affected individuals with rare CNVs (n 019), which may be the first full study of a subject from a large CMT1A family with nonrecurrent rearrangement. The clinical phenotype showed no significant difference compared with common CMT1A patients, but with variable phenotypes. In particular, a broad intrafamilial phenotypic spectrum was observed within the same family, which may suggest the existence of a genetic modifier. This study may broaden the understanding of the role of CNVs in the pathogenesis of CMT.

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X-linked Charcot-Marie-Tooth disease with connexin 32 mutations

Cited by 166 publications

References 13 publications

Transgenic Expression of HumanConnexin32in Myelinating Schwann Cells Prevents Demyelination inConnexin32-Null Mice

Transgenic Expression of HumanConnexin32in Myelinating Schwann Cells Prevents Demyelination inConnexin32-Null Mice

Intermediate Charcot-Marie-Tooth disease

Wide phenotypic variations in Charcot-Marie-Tooth 1A neuropathy with rare copy number variations on 17p12

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