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MFN2 gene

mitofusin 2
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Normal Function

The MFN2 gene provides instructions for making a protein called mitofusin 2. This protein helps determine the shape and structure (morphology) of mitochondria, the energy-producing centers within cells. Mitofusin 2 is made in many types of cells and tissues, including muscles, the spinal cord, and the nerves that connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound (peripheral nerves).

Within cells, mitofusin 2 is found in the outer membrane that surrounds mitochondria. Mitochondria are dynamic structures that undergo changes in morphology through processes called fission (splitting into smaller pieces) and fusion (combining pieces). These changes in morphology are necessary for mitochondria to function properly. Mitofusin 2 helps to regulate the morphology of mitochondria by controlling the fusion process.

Health Conditions Related to Genetic Changes

Charcot-Marie-Tooth disease

Researchers have identified more than 100 MFN2 gene mutations that cause a form of Charcot-Marie-Tooth disease known as type 2A. Charcot-Marie-Tooth disease damages the peripheral nerves, which can result in loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands.

Almost all of the MFN2 gene mutations that cause Charcot-Marie-Tooth disease change single protein building blocks (amino acids) in mitofusin 2. These changes alter a critical region in mitofusin 2, and the protein cannot function properly. A few mutations create a premature stop signal in the instructions for making mitofusin 2. As a result, no protein is produced, or an abnormally small protein is made.

Several MFN2 gene mutations cause a variant of type 2A Charcot-Marie-Tooth disease that is characterized by particularly severe symptoms that begin before age 10 and include impaired vision. (This variant is also called hereditary motor and sensory neuropathy VI.) Vision loss is caused by the breakdown of the nerves that carry information from the eyes to the brain (optic atrophy).

It is unclear how MFN2 gene mutations lead to the nerve problems characteristic of type 2A Charcot-Marie-Tooth disease. Researchers suggest that mitochondria cannot fuse properly or move normally within the cell without functional mitofusin 2, which may disrupt the cell's energy supply. Nerve cells may be particularly sensitive to an interrupted supply of energy.

More About This Health Condition

Other Names for This Gene

  • CMT2A2
  • CPRP1
  • KIAA0214
  • MARF
  • MFN2_HUMAN
  • mitochondrial assembly regulatory factor

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Research Resources

References

  • Ando M, Hashiguchi A, Okamoto Y, Yoshimura A, Hiramatsu Y, Yuan J, Higuchi Y, Mitsui J, Ishiura H, Umemura A, Maruyama K, Matsushige T, Morishita S, Nakagawa M, Tsuji S, Takashima H. Clinical and genetic diversities of Charcot-Marie-Tooth disease with MFN2 mutations in a large case study. J Peripher Nerv Syst. 2017 Sep;22(3):191-199. doi: 10.1111/jns.12228. Epub 2017 Jul 30. Erratum in: J Peripher Nerv Syst. 2018 Jun;23(2):149-150. Citation on PubMed or Free article on PubMed Central
  • Baloh RH, Schmidt RE, Pestronk A, Milbrandt J. Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth disease from mitofusin 2 mutations. J Neurosci. 2007 Jan 10;27(2):422-30. Citation on PubMed
  • Bombelli F, Stojkovic T, Dubourg O, Echaniz-Laguna A, Tardieu S, Larcher K, Amati-Bonneau P, Latour P, Vignal O, Cazeneuve C, Brice A, Leguern E. Charcot-Marie-Tooth disease type 2A: from typical to rare phenotypic and genotypic features. JAMA Neurol. 2014 Aug;71(8):1036-42. doi: 10.1001/jamaneurol.2014.629. Review. Citation on PubMed
  • Cartoni R, Martinou JC. Role of mitofusin 2 mutations in the physiopathology of Charcot-Marie-Tooth disease type 2A. Exp Neurol. 2009 Aug;218(2):268-73. doi: 10.1016/j.expneurol.2009.05.003. Epub 2009 May 8. Review. Citation on PubMed
  • Choi BO, Nakhro K, Park HJ, Hyun YS, Lee JH, Kanwal S, Jung SC, Chung KW. A cohort study of MFN2 mutations and phenotypic spectrums in Charcot-Marie-Tooth disease 2A patients. Clin Genet. 2015 Jun;87(6):594-8. doi: 10.1111/cge.12432. Epub 2014 Jun 18. Citation on PubMed
  • Chung KW, Kim SB, Park KD, Choi KG, Lee JH, Eun HW, Suh JS, Hwang JH, Kim WK, Seo BC, Kim SH, Son IH, Kim SM, Sunwoo IN, Choi BO. Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations. Brain. 2006 Aug;129(Pt 8):2103-18. Epub 2006 Jul 10. Citation on PubMed
  • Kijima K, Numakura C, Izumino H, Umetsu K, Nezu A, Shiiki T, Ogawa M, Ishizaki Y, Kitamura T, Shozawa Y, Hayasaka K. Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth neuropathy type 2A. Hum Genet. 2005 Jan;116(1-2):23-7. Epub 2004 Nov 11. Citation on PubMed
  • Ouvrier R, Grew S. Mechanisms of disease and clinical features of mutations of the gene for mitofusin 2: an important cause of hereditary peripheral neuropathy with striking clinical variability in children and adults. Dev Med Child Neurol. 2010 Apr;52(4):328-30. doi: 10.1111/j.1469-8749.2010.03613.x. Epub 2010 Feb 12. Review. Citation on PubMed
  • Pareyson D, Saveri P, Sagnelli A, Piscosquito G. Mitochondrial dynamics and inherited peripheral nerve diseases. Neurosci Lett. 2015 Jun 2;596:66-77. doi: 10.1016/j.neulet.2015.04.001. Epub 2015 Apr 3. Review. Citation on PubMed
  • Stuppia G, Rizzo F, Riboldi G, Del Bo R, Nizzardo M, Simone C, Comi GP, Bresolin N, Corti S. MFN2-related neuropathies: Clinical features, molecular pathogenesis and therapeutic perspectives. J Neurol Sci. 2015 Sep 15;356(1-2):7-18. doi: 10.1016/j.jns.2015.05.033. Epub 2015 May 29. Review. Citation on PubMed
  • Tan CA, Rabideau M, Blevins A, Westbrook MJ, Ekstein T, Nykamp K, Deucher A, Harper A, Demmer L. Autosomal recessive MFN2-related Charcot-Marie-Tooth disease with diaphragmatic weakness: Case report and literature review. Am J Med Genet A. 2016 Jun;170(6):1580-4. doi: 10.1002/ajmg.a.37611. Epub 2016 Mar 8. Review. Citation on PubMed
  • Züchner S, De Jonghe P, Jordanova A, Claeys KG, Guergueltcheva V, Cherninkova S, Hamilton SR, Van Stavern G, Krajewski KM, Stajich J, Tournev I, Verhoeven K, Langerhorst CT, de Visser M, Baas F, Bird T, Timmerman V, Shy M, Vance JM. Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. Ann Neurol. 2006 Feb;59(2):276-81. Citation on PubMed
  • Züchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, Zappia M, Nelis E, Patitucci A, Senderek J, Parman Y, Evgrafov O, Jonghe PD, Takahashi Y, Tsuji S, Pericak-Vance MA, Quattrone A, Battaloglu E, Polyakov AV, Timmerman V, Schröder JM, Vance JM. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet. 2004 May;36(5):449-51. Epub 2004 Apr 4. Erratum in: Nat Genet. 2004 Jun;36(6):660. Battologlu E [corrected to Battaloglu E]. Citation on PubMed
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