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01-02-2012 | Original Article

Vincristine exacerbates asymptomatic Charcot–Marie–Tooth disease with a novel EGR2 mutation

Authors: Tomonori Nakamura, Akihiro Hashiguchi, Shinsuke Suzuki, Kimiharu Uozumi, Shoko Tokunaga, Hiroshi Takashima

Published in: Neurogenetics | Issue 1/2012

Abstract

Neurotoxicity is a common side effect of vincristine (VCR) treatment. Severe exacerbations of neuropathy have been reported in patients with Charcot–Marie–Tooth disease (CMT) 1A with duplication of the peripheral myelin protein 22 (PMP22) gene. However, whether or not VCR exacerbates neuropathies through mutations in other CMT-associated genes besides PMP22 duplication has not been well studied. The purpose of this study was to identify mutations in any CMT-associated genes in a patient with hypersensitivity to VCR. We performed clinical, electrophysiological, and genetic examinations of a 23-year-old woman, who was hypersensitive to low-dose VCR, and her healthy mother. DNA analysis was performed using our specially designed resequencing array that simultaneously screens for 28 CMT-associated genes. Electrophysiological studies revealed that the patient and her healthy mother had demyelinating polyneuropathy. Furthermore, they showed the same novel mutation in the early growth response 2 (EGR2) gene. Recognizing pre-existing asymptomatic CMT by electrophysiological studies and genetic analysis before VCR treatment allowed us to prevent severe VCR-induced neuropathy.

Weiss HD, Walker MD, Wiernik PH (1974) Neurotoxicity of commonly used antineoplastic agents (second of two parts). N Engl J Med 291:127–133PubMedCrossRef

Trobaugh-Lotrario AD, Smith AA, Odom LF (2003) Vincristine neurotoxicity in the presence of hereditary neuropathy. Med Pediatr Oncol 40:39–43PubMedCrossRef

Weimer LH, Podwall D (2006) Medication-induced exacerbation of neuropathy in Charcot–Marie–Tooth disease. J Neurol Sci 242:47–54PubMedCrossRef

Birouk N, Gouider R, Le Guern E, Gugenheim M, Tardieu S, Maisonobe T, Le Forestier N, Agid Y, Brice A, Bouche P (1997) Charcot–Marie–Tooth disease type 1A with 17p11.2 duplication. Clinical and electrophysiological phenotype study and factors influencing disease severity in 119 cases. Brain 120:813–823PubMedCrossRef

Boerkoel CF, Takashima H, Garcia CA, Olney RK, Johnson J, Berry K, Russo P, Kennedy S, Teebi AS, Scavina M, Williams LL, Mancias P, Butler IJ, Krajewski K, Shy M, Lupski JR (2002) Charcot–Marie–Tooth disease and related neuropathies: mutation distribution and genotype–phenotype correlation. Ann Neurol 51:190–201PubMedCrossRef

Yerushalmi R, Levi I, Wygoda M, Ifergane G, Wirguin I (2007) Are platinum-based chemotherapeutic drugs safe for patients with Charcot–Marie–Tooth disease? J Peripher Nerv Syst 12:139–141PubMedCrossRef

Neumann Y, Toren A, Rechavi G, Seifried B, Shoham NG, Mandel M, Kenet G, Sharon N, Sadeh M, Navon R (1996) Vincristine treatment triggering the expression of asymptomatic Charcot–Marie–Tooth disease. Med Pediatr Oncol 26:280–283PubMedCrossRef

Mercuri E, Poulton J, Buck J, Broadbent V, Bamford M, Jungbluth H, Manzur AY, Muntoni F (1999) Vincristine treatment revealing asymptomatic hereditary motor sensory neuropathy type 1A. Arch Dis Child 81:442–443PubMedCrossRef

Uno S, Katayama K, Dobashi N, Hirano A, Ogihara A, Yamazaki H, Usui N, Kobayashi T, Inoue K, Kuraishi Y (1999) Acute vincristine neurotoxicity in a non-Hodgkin's lymphoma patient with Charcot–Marie–Tooth disease. Rinsho Ketsueki 40:414–419PubMed

10.

Hildebrandt G, Holler E, Woenkhaus M, Quarch G, Reichle A, Schalke B, Andreesen R (2000) Acute deterioration of Charcot–Marie–Tooth disease IA (CMT IA) following 2 mg of vincristine chemotherapy. Ann Oncol 11:743–747PubMedCrossRef

11.

Naumann R, Mohm J, Reuner U, Kroschinsky F, Rautenstrauss B, Ehninger G (2001) Early recognition of hereditary motor and sensory neuropathy type 1 can avoid life-threatening vincristine neurotoxicity. Br J Haematol 115:323–325PubMedCrossRef

12.

Cil T, Altintas A, Tamam Y, Battaloglu E, Isikdogan A (2009) Low dose vincristine-induced severe polyneuropathy in a Hodgkin lymphoma patient: a case report (vincristine-induced severe polyneuropathy). J Pediatr Hematol Oncol 31:787–789PubMedCrossRef

13.

Ajitsaria R, Reilly M, Anderson J (2008) Uneventful administration of vincristine in Charcot–Marie–Tooth disease type 1X. Pediatr Blood Cancer 50:874–876PubMedCrossRef

14.

Nishikawa T, Kawakami K, Kumamoto T, Tonooka S, Abe A, Hayasaka K, Okamoto Y, Kawano Y (2008) Severe neurotoxicities in a case of Charcot–Marie–Tooth disease type 2 caused by vincristine for acute lymphoblastic leukemia. J Pediatr Hematol Oncol 30:519–521PubMedCrossRef

15.

Porter CC, Carver AE, Albano EA (2009) Vincristine induced peripheral neuropathy potentiated by voriconazole in a patient with previously undiagnosed CMT1X. Pediatr Blood Cancer 52:298–300PubMedCrossRef

16.

Nagarajan R, Svaren J, Le N, Araki T, Watson M, Milbrandt J (2001) EGR2 mutations in inherited neuropathies dominant-negatively inhibit myelin gene expression. Neuron 30:355–368PubMedCrossRef

17.

Scherer SS (1997) The biology and pathobiology of Schwann cells. Curr Opin Neurol 10:386–397PubMedCrossRef

18.

Niemann A, Berger P, Suter U (2006) Pathomechanisms of mutant proteins in Charcot–Marie–Tooth disease. Neuromolecular Med 8:217–242PubMedCrossRef

19.

Swiatek PJ, Gridley T (1993) Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20. Gene Dev 7:2071–2084PubMedCrossRef

20.

Topilko P, Schneider-Maunoury S, Levi G, Baron-Van Evercooren A, Chennoufi AB, Seitanidou T, Babinet C, Charnay P (1994) Krox-20 controls myelination in the peripheral nervous system. Nature 371:796–799PubMedCrossRef

21.

Warner LE, Mancias P, Butler IJ, McDonald CM, Keppen L, Koob KG, Lupski JR (1998) Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. Nat Genet 18:382–384PubMedCrossRef

22.

Timmerman V, De Jonghe P, Ceuterick C, De Vriendt E, Lofgren A, Nelis E, Warner LE, Lupski JR, Martin JJ, Van Broeckhoven C (1999) Novel missense mutation in the early growth response 2 gene associated with Dejerine–Sottas syndrome phenotype. Neurology 52:1827–1832PubMed

23.

Warner LE, Svaren J, Milbrandt J, Lupski JR (1999) Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies. Hum Mol Genet 8:1245–1251PubMedCrossRef

24.

Boerkoel C, Takashima H, Bacino C, Daentl D, Lupski J (2001) EGR2 mutation R359W causes a spectrum of Dejerine–Sottas neuropathy. Neurogenetics 3:153–157PubMedCrossRef

25.

Yoshihara T, Kanda F, Yamamoto M, Ishihara H, Misu K, Hattori N, Chihara K, Sobue G (2001) A novel missense mutation in the early growth response 2 gene associated with late-onset Charcot–Marie–Tooth disease type 1. J Neurol Sci 184:149–153PubMedCrossRef

26.

Mikesova E, Huhne K, Rautenstrauss B, Mazanec R, Barankova L, Vyhnalek M, Horacek O, Seeman P (2005) Novel EGR2 mutation R359Q is associated with CMT type 1 and progressive scoliosis. Neuromuscul Disord 15:764–767PubMedCrossRef

27.

Jang SW, LeBlanc SE, Roopra A, Wrabetz L, Svaren J (2006) In vivo detection of Egr2 binding to target genes during peripheral nerve myelination. J Neurochem 98:1678–1687PubMedCrossRef

28.

LeBlanc SE, Ward RM, Svaren J (2007) Neuropathy-associated Egr2 mutants disrupt cooperative activation of myelin protein zero by Egr2 and Sox10. Mol Cell Biol 27:3521–3529PubMedCrossRef

29.

Jang SW, Svaren J (2009) Induction of myelin protein zero by early growth response 2 through upstream and intragenic elements. J Biol Chem 284:20111–20120PubMedCrossRef

30.

Jones EA, Lopez-Anido C, Srinivasan R, Krueger C, Chang LW, Nagarajan R, Svaren J (2011) Regulation of the PMP22 gene through an intronic enhancer. J Neurosci 31:4242–4250PubMedCrossRef

Title: Vincristine exacerbates asymptomatic Charcot–Marie–Tooth disease with a novel EGR2 mutation
Authors: Tomonori Nakamura
Akihiro Hashiguchi
Shinsuke Suzuki
Kimiharu Uozumi
Shoko Tokunaga
Hiroshi Takashima
Publication date: 01-02-2012
Publisher: Springer-Verlag
Published in: Neurogenetics / Issue 1/2012
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-012-0313-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Vincristine exacerbates asymptomatic Charcot–Marie–Tooth disease with a novel EGR2 mutation

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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