1 X-linked Charcot-Marie-Tooth disease

An X-linked dominant form of Charcot-Marie-Tooth Disease that is characterized by severely reduced motor nerve conduction velocities (NCV) (less than 38 m/s) and segmental DEMYELINATION and remyelination with onion bulb formations on nerve biopsy. Mutations in the GJB1 gene have been identified.

Also Known As:

Charcot-Marie-Tooth disease, X-linked, 1; CMTX 1; Charcot-Marie-Tooth Neuropathy, X-Linked, 1; Charcot-Marie-Tooth peroneal muscular atrophy, X-linked; Cmtx1; HMSN, X-linked; Hereditary motor and sensory neuropathy, X-linked

Networked: 42 relevant articles (0 outcomes, 3 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Charcot-Marie-Tooth Disease (Peroneal Muscular Atrophy)
2.	Necrosis
3.	Genomic Instability
4.	Hereditary Sensory and Motor Neuropathy (Dejerine Sottas Disease)
5.	Inherited Peripheral Neuropathy

Experts

1.	Li, Qu: 2 articles (01/2021 - 01/2020)
2.	Liu, Xu: 2 articles (01/2021 - 01/2020)
3.	Pareyson, Davide: 2 articles (04/2017 - 06/2014)
4.	Piscosquito, Giuseppe: 2 articles (04/2017 - 06/2014)
5.	Saveri, Paola: 2 articles (04/2017 - 06/2014)
6.	Hao, Yong: 2 articles (07/2016 - 06/2011)
7.	Altié, Alexandre: 2 articles (01/2016 - 05/2015)
8.	Bihel, Frederic: 2 articles (01/2016 - 05/2015)
9.	Bordignon, Benoit: 2 articles (01/2016 - 05/2015)
10.	Fontes, Michel: 2 articles (01/2016 - 05/2015)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to 1 X-linked Charcot-Marie-Tooth disease:

1.	ConnexinsIBA 01/01/2019 - "CMT1A, CMT1B, and CMTX1 are the common forms of CMT, which are attributed to the genes encoding the myelin or gap junction proteins expressed in the myelinating Schwann cells. " 01/01/2019 - "Gap junction protein beta-1 (GJB1) gene mutations lead to X-linked Charcot-Marie-Tooth Type 1 (CMTX1). " 09/01/2015 - "The X-linked form, CMTX1, is caused by mutations in the gap junction protein beta 1 (GJB1) gene, expressed both by peripheral Schwann cells and central oligodendrocytes. " 07/01/2014 - "Mutations in the connexin-32 gene (gap junction protein β1 [GJB1]) are responsible for CMTX1 disease. " 12/12/2006 - "To characterize a large family with X-linked Charcot-Marie-Tooth (CMT) neuropathy without mutations in the gap junction protein B1 (GJB1) gene, which has an unusual phenotype that is different in some aspects from classic CMTX1. "
2.	Myelin ProteinsIBA 02/01/1998 - "Charcot-Marie-Tooth disease: histopathological features of the peripheral myelin protein (PMP22) duplication (CMT1A) and connexin32 mutations (CMTX1)." 09/07/2007 - "To study whether the immune system is involved in the pathogenesis of CMTX1 patients and asymptomatic carriers, we measured serum concentrations of antibodies to peripheral nerve myelin protein 22 (PMP22), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) by ELISA. "
3.	Interleukin-6 (Interleukin 6)IBA 09/07/2007 - "There was no statistical difference in serum concentrations of IL-6 and TNF-alpha between CMTX1 patients and normal subjects. " 09/07/2007 - "Study of antibodies to PMP22, IL-6 and TNF-alpha concentrations in serum in a CMTX1 family." 09/07/2007 - "To study whether the immune system is involved in the pathogenesis of CMTX1 patients and asymptomatic carriers, we measured serum concentrations of antibodies to peripheral nerve myelin protein 22 (PMP22), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) by ELISA. "
4.	Tumor Necrosis Factor-alpha (Tumor Necrosis Factor)IBA 09/07/2007 - "There was no statistical difference in serum concentrations of IL-6 and TNF-alpha between CMTX1 patients and normal subjects. " 09/07/2007 - "Study of antibodies to PMP22, IL-6 and TNF-alpha concentrations in serum in a CMTX1 family." 09/07/2007 - "To study whether the immune system is involved in the pathogenesis of CMTX1 patients and asymptomatic carriers, we measured serum concentrations of antibodies to peripheral nerve myelin protein 22 (PMP22), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) by ELISA. "
5.	Messenger RNA (mRNA)IBA 01/01/1998 - "We report the results of molecular studies in a CMTX1 Italian family, in which the mutation, found in the 5'-UTR, resulted in an abnormal mRNA connexin-32 expression. " 01/01/1998 - "Mutation in the nerve-specific 5'non-coding region of Cx32 gene and absence of specific mRNA in a CMTX1 Italian family. "
6.	AntibodiesIBA 09/07/2007 - "Our results also indicated that anti-PMP22 antibodies in the CMTX1 family varied with sex. " 09/07/2007 - "Study of antibodies to PMP22, IL-6 and TNF-alpha concentrations in serum in a CMTX1 family." 09/07/2007 - "To study whether the immune system is involved in the pathogenesis of CMTX1 patients and asymptomatic carriers, we measured serum concentrations of antibodies to peripheral nerve myelin protein 22 (PMP22), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) by ELISA. "
7.	Gap Junction beta-1 ProteinIBA 01/01/2020 - "Background: X-linked Charcot-Marie-Tooth type 1 (CMTX1) is the second most frequent form of CMT, which is caused by mutations in the gap junction beta 1 gene (GJB1) coding for connexin 32 protein. " 07/01/2016 - "CNS involvement in CMTX1 caused by a novel connexin 32 mutation: a 6-year follow-up in neuroimaging and nerve conduction." 06/01/2014 - "X-linked Charcot-Marie-Tooth type 1 (CMTX1) is the second most common type of CMT and is caused by mutations in the Gap-Junction Beta-1 gene (GJB1), encoding connexin 32 which is expressed in Schwann cells as well as in oligodendrocytes. " 02/01/2011 - "The diagnosis of CMTX was based on an identifiable connexin 32 mutation (CMTX1) or a consistent pedigree and neurophysiologic features in children without a connexin 32 mutation (CMTX-other). " 07/01/2010 - "X-linked hereditary motor sensory neuropathy type 1 (CMTX 1) is caused by mutation in the GJB1 gene that codes for the connexin 32 protein. "
8.	Proteins (Proteins, Gene)FDA Link 01/01/2021 - "X-linked Charcot-Marie-Tooth type 1 (CMTX1) is an inherited peripheral neuropathy caused by mutations in the gap junction beta 1 (GJB1) gene, which encodes the connexin32 protein. " 11/01/2016 - "Charcot-Marie-Tooth disease type X1 (CMTX1), which is caused by mutations in the gap junction (GJ) protein beta-1 gene (GJB1), is the second most common form of Charcot-Marie-Tooth disease (CMT). " 01/01/1999 - "Recently, the consequences of missing or defective connexin proteins were studied in human patients with defects in connexin32 (Cx32; beta 1; X-linked Charcot-Marie-Tooth disease) or in Cx26 (beta 2; non-syndromic sensorineural deafness), and in mice with targeted deletions in the Cx26, Cx32, Cx37 (alpha 4), Cx43 (alpha 1), Cx46 (alpha 3) or Cx50 (alpha 8) genes. "
9.	Calcium-Calmodulin-Dependent Protein Kinase Type 2IBA 05/07/2015 - "Our data demonstrate that fibroblasts from CMTX1 patients present a phenotype similar to transgenic lines that can be corrected by CamKII inhibitors. " 05/07/2015 - "We cultured fibroblasts from skin biopsies of CMTX1 patients and analyzed cells for genomic instabilty, connexon activity, and potential correction by CamKII inhibitors. " 01/25/2016 - "Erratum to: CMTX1 patients' cells present genomic instability corrected by CamKII inhibitors." 05/07/2015 - "CMTX1 patients' cells present genomic instability corrected by CamKII inhibitors."
10.	3' Untranslated Regions (3' UTR)IBA 01/01/2018 - "The c.15C>T mutation in the GJB1 3' UTR segregates with CMTX1 in 8 generations. " 04/11/2017 - "A novel mutation, c.15C>T, was detected in the 3' UTR of GJB1 in 2 unrelated families with CMTX1 and is the first pathogenic mutation in the 3'UTR of any myelin-associated CMT gene. "

Therapies and Procedures

1.	Therapeutics 02/10/2023 - "We examined if 1 to 5 months of daily cemdomespib therapy may improve neuropathic symptoms in three mouse models of CMTX1 (Cx32 deficient (Cx32def), T55I-Cx32def, and R75W-Cx32 mice). " 02/10/2023 - "CMTX1 currently lacks a pharmacologic approach toward disease management, and we have previously shown that modulating the expression of molecular chaperones using novologue therapy may provide a viable disease-modifying approach to treat metabolic and demyelinating neuropathies. "
2.	Ligation 01/01/2020 - "Overall, the diagnostic yield of the combined strategy of Multiplex-ligation-dependent-probe-amplification (MLPA) of PMP22/GJB1/MPZ and GJB1/MPZ/PMP22 Sanger sequencing was 63.6% (28/44) for index cases with demyelinating/intermediate CMT suspicion (21 CMT1A-PMP22, 5 CMTX1-GJB1 and 2 with probably CMT1B-MPZ diagnosis). "