How to assess the pathogenicity of mutations in Charcot-Marie-Tooth disease and other diseases?

• Autorzy: Kochanski A
• Języki publikacji: EN

Abstrakty

EN

Knowledge whether a certain DNA variant is a pathogenic mutation or a harmless polymorphism is a critical issue in medical genetics, in which results of a molecular analysis may serve as a basis for diagnosis and genetic counseling. Due to its genetic heterogeneity expressed at the levels of loci, genes and mutations, Charcot-Marie-Tooth (CMT) disease can serve as a model group of clinically homogenous diseases for studying the pathogenicity of mutations. Close to a 17p11.2-p12 duplication occurring in 70% of patients with the demyelinating form of CMT disease, numerous mutations have been identified in poorly characterized genes coding for proteins of an unknown function. Functional analyses, segregation analyses of large pedigrees, and inclusion of large control groups are required to assess the potential pathogenicity of CMT mutations. Hence, the pathogenicity of numerous CMT mutations remains unclear. Some variants detected in the CMT genes and originally described as pathogenic mutations have been shown to have a polymorphic character. In contrast, polymorphisms initially considered harmless were later reclassified as pathogenic mutations. However, the process of assessing the pathogenicity of mutations, as presented in this study for CMT disorders, is a more general issue concerning all disorders with a genetic background. Since the number of DNA variants is still growing, in the near future geneticists will increasingly have to cope with the problem of pathogenicity of identified genetic variants.

Słowa kluczowe

EN

human disease; Charcot-Marie-Tooth disease; segregation analysis; harmless polymorphism; medical genetics; pathogenicity; functional analysis; mutation; pathogenic mutation

• Wydawca: -
• Czasopismo: Journal of Applied Genetics
• Rocznik: 2006
• Tom: 47
• Numer: 3
• Opis fizyczny: p.255-260,ref.

Twórcy

autor

Kochanski A

• Neuromuscular Unit, Mossakowski Medical Research Center, Pawinskiego 5, 02-106 Warsaw, Poland

Bibliografia

• Andrigo C, Boito C, Prandini P, Mostacciuolo ML, Siciliano G, Angelini C, Pegoraro E, 2005. A novel out-of-frame mutation in the neurofilament light chain gene (NEFL) does not result in Charcot-Marie-Tooth disease type 2E. Neurogenetics 6:49-50.
• Beauvais K, Furby A, Latour P, 2006. Clinical, electrophysiological and molecular genetic studies in a family with X-linked dominant Charcot-Marie-Tooth neuropathy presenting a novel mutation in GJB1 promoter and a rare polymorphism in LITAF/SIMPLE. Neuromusc Disord 16: 14-18.
• Ben Othmane K, Middleton LT, Loprest LJ, Wilkinson KM, Lennon F, Rozear MP, et al. 1993. Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity. Genomics 17: 370-375.
• Bennett CL, Shirk AJ, Huyhn HM, Street VA, Nelis E, Van Maldergem L, et al. 2004. SIMPLE mutations in demyelinating neuropathy and distribution in sciatic nerve. Ann Neurol 55: 713-720.
• Bissar-Tadmouri N, Nelis E, Züchner S, Parman Y, Deymeer F, Serdaroglu P, et al. 2004. Absence of KIF1B mutation in a large Turkish CMT2A family suggests involvement of a second gene. Neurology 62: 1522-1525.
• Fabbretti E, Edomi P, Brancolini C, Schneider C, 1995. Apoptotic phenotype induced by overexpression of wild-type gas3/PMP22: its relation to the demyelinating peripheral neuropathy CMT1A. Genes Dev 9: 1846-1856.
• Ford EB, 1957. Polymorphism in plants, animals and man. Nature 180: 1315-1319.
• Harding AE, Thomas PK, 1980. Genetic aspects of hereditary motor and sensory neuropathy (types I and II). J Med Genet 17: 329-336.
• Inherited Peripheral Neuropathy Mutation Database www.molgen.ua.ac.be/CMTMutations.
• Jordanova A, De Jonghe P, Boerkoel CF, Takashima H, De Vriendt E, Ceuterick C, et al. 2003. Mutations in the neurofilament light gene (NEFL) cause early-onset severe Charcot-Marie-Tooth disease. Brain 126: 590-597.
• Kabzińska D, Perez-Olle R, Goryunov D, Drac H, Ryniewicz B, Hausmanowa-Petrusewicz I, et al. 2006. Charcot-Marie-Tooth disease associated with a novel I214M substitution in the NEFL gene. A functional analysis using cell culture models. J Peripher Nerv Syst (in press).
• Lehmann-Horn F, 2004. Disease-causing mutations or functional polymorphisms? Acta Myol 23: 85-89.
• Mersiyanova IV, Perepelov AV, Polyakov AV, Sitnikov VF, Dadali EL, Oparin RB, et al. 2000. A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament light gene. Am J Hum Genet 67: 37-46.
• Mitchell AA, Chakravarti A, Cutler DJ, 2005. On the probability that a novel variant is a disease-causing mutation. Genome Res 15: 960-966.
• Mitchell AL, Elson JL, Howell N, Taylor RW, Turnbull DM, 2006. Sequence variation in mitochondrial complex I genes: mutation or polymorphism? J Med Genet 43: 175-179.
• Moriwaki Y, Begum NA, Kobayashi M, Matsumoto M, Toyoshima K, Seya T, 2001. Mycobacterium bovis Bacillus Calmette-Guerin and its cell wall complex induce a novel lysosomal membrane protein, SIMPLE, that bridges the missing link between lipopolysaccharide and p-53 inducible gene, LITAF (PIG7), and estrogen-inducible gene, EET-1. J Biol Chem 276: 23065-23076.
• Muller HW, 2000. Tetraspan myelin protein PMP22 and demyelinating peripheral neuropathies: new facts and hypotheses. Glia 29: 182-185.
• Naef R, Suter U, 1999. Impaired intracellular trafficking is a common disease mechanism of PMP22 point mutations in peripheral neuropathies. Neurobiol Dis 6: 1-14.
• Nelis E, Holmberg В, Adolfsson R, Holmgren G, Van Broeckhoven C, 1997. PMP22 Thr(118)Met: recessive CMT1 mutation or polymorphism? Nat Genet 15: 13-14.
• Perez-Olle R, Jones ST, Liem RK, 2004. Phenotypic analysis of neurofilament light gene mutations linked to Charcot-Marie-Tooth disease in cell culture models. Hum Mol Genet 13: 2207-2220.
• Perez-Olle R, Lopez-Toledano MA, Liem RK, 2004. The G336S variant in the human neurofilament-M gene does not affect its assembly or distribution: Importance of the functional analysis of neurofilament variants. J Neuropathol Exp Neurol 63: 759-774.
• Roa BB, Garcia CA, Pentao L, Killian JM, Trask BJ, Suter U, et al. 1993. Evidence for a recessive PMP22 mutation in Charcot-Marie-Tooth disease type 1 A. Nat Genet 5: 189-194.
• Saifi GM, Szigeti K, Wiszniewski W, Shy ME, Krajewski K, Hausmanowa-Petrusewicz I, et al. 2005. SIMPLE mutations in Charcot-Marie-Tooth disease and the potential role of its protein product in protein degradation. Hum Mutat 25: 372-383.
• Saito M, Hayashi Y, Suzuki T, Tanaka H, Hozumi I, Tsuji S, 1997. Linkage mapping of the gene for Charcot-Marie-Tooth disease type 2 to chromosome 1p (CMT2A) and the clinical features of CMT2A. Neurology 49: 1630-1635.
• Shy ME, Scavina MT, Clark A, Krajewski KM, Li J, Kamholz J, et al. 2006. T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy. Ann Neurol 59: 358-364.
• Snipes GJ, Suter U, Welcher AA, Shooter EM, 1992. Characterization of a novel peripheral nervous system myelin protein (PMP22/SR13). J Cell Biol 117: 225-238.
• Street VA, Bennett CL, Goldy JD, Shirk AJ, Kleopa KA, Tempel BL, et al. 2003. Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C. Neurology 60: 22-26.
• Street VA, Goldy JD, Golden AS, Tempel BL, Bird TD, Chance PF, 2002. Mapping of Charcot- Marie-Tooth type 1C to chromosome 16p identifies a novel locus for demyelinating neuropathies. Am J Hum Genet 70: 244-250.
• Suter U, Moskow JJ, Welcher AA, Snipes GJ, Kosaras В, Sidman RL, et al. 1992. A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse. Proc Natl Acad Sci USA 89: 4382-4386.
• Suter U, Snipes GJ, 1995. Peripheral myelin protein 22: facts and hypotheses. J Neurosci Res 40: 145-151.
• Verhoeven K, Claeys KG, Zuchner S, Schroder JM, Weis J, Ceuterick C, et al. 2006. MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain 19: Epub ahead of print.
• Yamamoto M, Yoshihara T, Hattori N, Sobue G, 2004. Glu528del in NEFL is a polymorphic variant rather than disease-causing mutation for Charcot-Marie-Tooth disease in Japan. Neurogenetics 5: 75-77.
• Zhao C, Takita J, Tanaka Y, Setou M, Nakagawa T, Takeda S, et al. 2001. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell 105: 587-597.
• Zuchner S, De Jonghe P, Jordanova A, Claeys KG, Guergueltcheva V, Cherninkova S, et al. 2006. Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. Ann Neurol 59: 276-281.
• Zuchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, et al. 2004. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet 36: 449-451.