Type 4B1 Charcot-Marie-Tooth disease

mutation in MTMR2

Also Known As:

Charcot-Marie-Tooth disease, Type 4B1; CMT4B; CMT4B1; Charcot-Marie-Tooth Disease, Autosomal Recessive, With Focally Folded Myelin Sheaths, Autosomal Recessive, Type 4b1; Charcot-Marie-Tooth Neuropathy, Type 4B1; Charcot-Marie-Tooth disease, Type 4B

Networked: 30 relevant articles (2 outcomes, 0 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Type 4B1 Charcot-Marie-Tooth disease
2.	Type 4B2 Charcot-Marie-Tooth disease
3.	Peripheral Nervous System Diseases (PNS Diseases)
4.	Congenital Structural Myopathies (Centronuclear Myopathy)
5.	Hereditary Sensory and Motor Neuropathy (Dejerine Sottas Disease)

Experts

1.	Bolino, Alessandra: 7 articles (01/2021 - 01/2002)
2.	Robinson, Fred L: 5 articles (01/2022 - 09/2005)
3.	Berger, Philipp: 4 articles (02/2011 - 06/2002)
4.	Suter, Ueli: 4 articles (02/2011 - 06/2002)
5.	Schenone, Angelo: 3 articles (01/2021 - 06/2015)
6.	Previtali, Stefano C: 3 articles (01/2019 - 07/2003)
7.	Dixon, Jack E: 3 articles (03/2008 - 09/2005)
8.	Quattrini, Angelo: 3 articles (09/2007 - 07/2003)
9.	Wrabetz, Lawrence: 3 articles (09/2005 - 01/2002)
10.	Bolino, A: 3 articles (05/2003 - 05/2000)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Type 4B1 Charcot-Marie-Tooth disease:

1.	phosphatidylinositol 3,5-diphosphateIBA 01/01/2021 - "Consistent with this, pharmacological inhibition of PtdIns(3,5)P2 synthesis or mTORC1/RhoA signaling ameliorates CMT4B1 phenotypes. " 01/01/2021 - "MTMR2 is a ubiquitously expressed catalytically active 3-phosphatase, which in vitro dephosphorylates the 3-phosphoinositides PtdIns3P and PtdIns(3,5)P2, with a preference for PtdIns(3,5)P2 A hallmark of CMT4B1 neuropathy are redundant loops of myelin in the nerve termed myelin outfoldings, which can be considered the consequence of altered growth of myelinated fibers during postnatal development. " 06/15/2002 - "We show that phosphatidylinositol-3-phosphate is also a substrate for Mtmr2, but, unlike myotubularin, Mtmr2 dephosphorylates phosphatidylinositol 3,5-bisphosphate with high efficiency and peak activity at neutral pH. We demonstrate that the known disease-associated MTMR2 mutations lead to dramatically reduced phosphatase activity, suggesting that the MTMR2 phosphatase activity is crucial for the proper function of peripheral nerves in CMT4B1. " 04/15/2013 - "CMT4B results from mutations in either myotubularin-related protein 2 (MTMR2; CMT4B1) or MTMR13 (CMT4B2), phosphoinositide (PI) 3-phosphatases that dephosphorylate phosphatidylinositol 3-phosphate (PtdIns3P) and PtdIns(3,5)P2, lipids which regulate endo-lysosomal membrane traffic. "
2.	myotubularinIBA 01/01/2022 - "The form of Charcot-Marie-Tooth type 4B (CMT4B) disease caused by mutations in myotubularin-related 5 (MTMR5; also called SET binding factor 1, SBF1) shows a spectrum of axonal and demyelinating nerve phenotypes. " 01/01/2021 - "Charcot-Marie-Tooth type 4B1 (CMT4B1) is a severe autosomal recessive demyelinating neuropathy with childhood onset, caused by loss-of-function mutations in the myotubularin-related 2 (MTMR2) gene. " 11/15/2013 - "Charcot-Marie-Tooth type 4B1 (CMT4B1) is a rare autosomal recessive demyelinating neuropathy caused by mutation of the myotubularin-related 2 (MTMR2) gene. " 09/14/2005 - "Mutations in MTMR2, the myotubularin-related 2 gene, cause autosomal recessive Charcot-Marie-Tooth type 4B1 (CMT4B1). " 09/09/2005 - "CMT4B is caused by recessively inherited mutations in either myotubularin-related 2 (MTMR2) or MTMR13 (also called SET-binding factor 2). "
3.	Phosphoric Monoester Hydrolases (Phosphatases)IBA 01/01/2019 - "The clinical description of the new mutations reported here overlap with previously reported CMT4B1 phenotypes caused by mutations in the phosphatase domain of MTMR2, suggesting that nonsense MTMR2 mutations, which are predicted to result in loss or disruption of the phosphatase domain, are associated with a severe phenotype and loss of independent ambulation by the early twenties. " 04/15/2013 - "The CMT4B disease-causing phosphatases Mtmr2 and Mtmr13 localize to the Schwann cell cytoplasm and endomembrane compartments, where they depend upon each other to achieve wild-type levels of protein expression." 03/18/2003 - "Myotubularins are a family of Phosphatidylinositol 3-phosphate (PtdIns3P) phosphatases identified by the positional cloning of the MTM1 gene in patients suffering from X-linked myotubular myopathy and the MTMR2 gene in patients suffering from the demyelinating neuropathy Charcot-Marie-Tooth disease type 4B. " 06/15/2002 - "We show that phosphatidylinositol-3-phosphate is also a substrate for Mtmr2, but, unlike myotubularin, Mtmr2 dephosphorylates phosphatidylinositol 3,5-bisphosphate with high efficiency and peak activity at neutral pH. We demonstrate that the known disease-associated MTMR2 mutations lead to dramatically reduced phosphatase activity, suggesting that the MTMR2 phosphatase activity is crucial for the proper function of peripheral nerves in CMT4B1. " 02/01/2011 - "Charcot-Marie-Tooth disease type 4B is caused by mutations in the genes encoding either the lipid phosphatase myotubularin-related protein-2 (MTMR2) or its regulatory binding partner MTMR13/SBF2. "
4.	Mechanistic Target of Rapamycin Complex 1IBA 01/01/2021 - "Consistent with this, pharmacological inhibition of PtdIns(3,5)P2 synthesis or mTORC1/RhoA signaling ameliorates CMT4B1 phenotypes. "
5.	Proteins (Proteins, Gene)FDA Link 01/01/2019 - "Almost none of the mutations in the MTMR2 and MTMR13 genes, responsible for CMT4B1 and B2, respectively, influence the correlation between disease severity and age, in agreement with the hypothesis of a complete loss of function of MTMR2/13 proteins for such mutations. " 02/01/2011 - "The CMT4B disease-causing proteins MTMR2 and MTMR13/SBF2 regulate AKT signalling." 09/20/2007 - "In this review, we discuss recent findings on this interesting protein family with the main focus on MTMR2 and MTMR13 and their involvement in the biology of Schwann cell and CMT4B neuropathies." 09/20/2007 - "Loss of these proteins could lead to uncontrolled folding of myelin and, ultimately, to CMT4B. " 09/09/2005 - "Given the genetic association of both MTMR2 and MTMR13 with CMT4B, we investigated the biochemical relationship between these two proteins. "
6.	Phosphatidylinositols (Phosphatidylinositol)IBA 12/15/2007 - "Mice deficient in Mtmr13/Sbf2 together with known Mtmr2-deficient animals will be of major value to unravel the disease mechanism in CMT4B and to elucidate the critical functions of protein complexes that are involved in phosphoinositide-controlled processes in peripheral nerves." 01/01/2018 - "Charcot-Marie-Tooth Disorder Type 4B (CMT4B) is a demyelinating peripheral neuropathy caused by mutations in myotubularin-related (MTMR) proteins 2, 13, or 5 (CMT4B1/2/3), which regulate phosphoinositide turnover and endosomal trafficking. " 04/15/2013 - "CMT4B results from mutations in either myotubularin-related protein 2 (MTMR2; CMT4B1) or MTMR13 (CMT4B2), phosphoinositide (PI) 3-phosphatases that dephosphorylate phosphatidylinositol 3-phosphate (PtdIns3P) and PtdIns(3,5)P2, lipids which regulate endo-lysosomal membrane traffic. "
7.	phosphatidylinositol 3-phosphateIBA 01/01/2021 - "MTMR2 is a ubiquitously expressed catalytically active 3-phosphatase, which in vitro dephosphorylates the 3-phosphoinositides PtdIns3P and PtdIns(3,5)P2, with a preference for PtdIns(3,5)P2 A hallmark of CMT4B1 neuropathy are redundant loops of myelin in the nerve termed myelin outfoldings, which can be considered the consequence of altered growth of myelinated fibers during postnatal development. " 03/18/2003 - "Myotubularins are a family of Phosphatidylinositol 3-phosphate (PtdIns3P) phosphatases identified by the positional cloning of the MTM1 gene in patients suffering from X-linked myotubular myopathy and the MTMR2 gene in patients suffering from the demyelinating neuropathy Charcot-Marie-Tooth disease type 4B. " 04/15/2013 - "CMT4B results from mutations in either myotubularin-related protein 2 (MTMR2; CMT4B1) or MTMR13 (CMT4B2), phosphoinositide (PI) 3-phosphatases that dephosphorylate phosphatidylinositol 3-phosphate (PtdIns3P) and PtdIns(3,5)P2, lipids which regulate endo-lysosomal membrane traffic. "
8.	LipidsIBA 02/01/2011 - "Charcot-Marie-Tooth disease type 4B is caused by mutations in the genes encoding either the lipid phosphatase myotubularin-related protein-2 (MTMR2) or its regulatory binding partner MTMR13/SBF2. " 04/15/2013 - "CMT4B results from mutations in either myotubularin-related protein 2 (MTMR2; CMT4B1) or MTMR13 (CMT4B2), phosphoinositide (PI) 3-phosphatases that dephosphorylate phosphatidylinositol 3-phosphate (PtdIns3P) and PtdIns(3,5)P2, lipids which regulate endo-lysosomal membrane traffic. "
9.	Dual-Specificity PhosphatasesIBA 05/01/2000 - "Using a positional-cloning strategy, we identified in unrelated CMT4B patients mutations occurring in the gene MTMR2, encoding myotubularin-related protein-2, a dual specificity phosphatase (DSP)."
10.	Protein Isoforms (Isoforms)IBA 01/01/2016 - "Combined, our data warrant further investigation of the truncated MTMR2 protein isoform in Schwann cells and in CMT4B1 pathogenesis."