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Published in: Familial Cancer 1/2020

01-01-2020 | Vestibular Schwannoma | Short Communication

Neurofibromatosis type 2 discordance in monozygous twins

Authors: S. Amico, P. Smith, S. Tobi, M. Perry, A. Wallace, D. G. Evans

Published in: Familial Cancer | Issue 1/2020

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Abstract

Neurofibromatosis type 2 (NF2) is an autosomal dominant condition caused by pathogenic variants in the NF2 gene. The pathogenic variant is either inherited or obtained by de novo mutation, characterised by the presence of schwannomas, meningiomas and ependymomas. Here we report the presence of NF2 in one twin, with bilateral vestibular schwannomas and a pathogenic variant of the NF2 gene identified in both tumour and lymphocytes, while his monozygous brother remains asymptomatic. Imaging of the unaffected twin showed no tumour load and genetic testing via Sanger sequencing and Amplification Refractory Mutation System assay demonstrated low levels of expression of the NF2 variant in lymphocytes. Further testing on non-haemopoietic tissue showed little expression or absence of the pathogenic variant. Given there is no family history and the low level of the variant, we assume the pathogenic variant is a de novo mutation during embryogenesis. De novo mutations have been described as occurring at three possible time points in the creation of monozygous twins with different genetic make-up; prior to the twinning event, as a cause of the event, or after the twinning event. Of these options, we hypothesise that the discordance in the expression of the NF2 variant between these twins is likely due to a mutational event that occurred as a result of either of the latter two possibilities, between which we cannot determine. The pathogenic variant in lymphocytes was likely transferred between the twins through a shared blood supply in utero, and the non-haemopoietic samples that showed low levels of expression, were likely due to the presence of lymphocytic cells. Therefore, we have a discordance between monozygous twins at the NF2 gene.
Literature
2.
go back to reference Evans DG, Huson SM, Donnai D, Neary W, Blair V, Newton V, Harris R (1992) A clinical study of type 2 neurofibromatosis. Q J Med 84(304):603–618PubMed Evans DG, Huson SM, Donnai D, Neary W, Blair V, Newton V, Harris R (1992) A clinical study of type 2 neurofibromatosis. Q J Med 84(304):603–618PubMed
4.
go back to reference Kluwe L, Mautner V, Heinrich B, Dezube R, Jacoby LB, Friedrich RE, MacCollin M (2003) Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas. J Med Genet 40(2):109–114CrossRef Kluwe L, Mautner V, Heinrich B, Dezube R, Jacoby LB, Friedrich RE, MacCollin M (2003) Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas. J Med Genet 40(2):109–114CrossRef
5.
go back to reference Machiela MJ, Zhou W, Sampson JN, Dean MC, Jacobs KB, Black A, Brinton LA, Chang IS, Chen C, Chen C, Chen K, Cook LS, Crous Bou M, De Vivo I, Doherty J, Friedenreich CM, Gaudet MM, Haiman CA, Hankinson SE, Hartge P, Henderson BE, Hong Y-C, Hosgood I HD III, Hsiung CA, Hu W, Hunter DJ, Jessop L, Kim HN, Kim YH, Kim YT, Klein R, Kraft P, Lan Q, Lin D, Liu J, Le Marchand L, Liang X, Lissowska J, Lu L, Magliocco AM, Matsuo K, Olson SH, Orlow I, Park JY, Pooler L, Prescott J, Rastogi R, Risch HA, Schumacher F, Seow A, Setiawan VW, Shen H, Sheng X, Shin M-H, Shu X-O, VanDen Berg D, Wang J-C, Wentzensen N, Wong MP, Wu C, Wu T, Wu Y-L, Xia L, Yang HP, Yang P-C, Zheng W, Zhou B, Abnet CC, Albanes D, Aldrich MC, Amos C, Amundadottir LT, Berndt SI, Blot WJ, Cathryn CH, Bracci PM, Burdett L, Buring JE, Butler MA, Carreón T, Chatterjee N, Chung CC, Cook MB, Cullen M, Davis FG, Ding T, Duell EJ, Epstein CG, Fan J-H, Figueroa JD, Fraumeni JF Jr., Freedman ND, Fuchs CS, Gao Y-T, Gapstur SM, Patiño-Garcia A, Garcia-Closas M, Gaziano JM, Giles GG, Gillanders EM, Giovannucci EL, Goldin L, Goldstein AM, Greene MH, Hallmans G, Harris CC, Henriksson R, Holly EA, Hoover RN, Hu N, Hutchinson A, Jenab M, Johansen C, Khaw K-T, Koh W-P, Laurence LN, Kooperberg C, Krogh V, Kurtz RC, LaCroix A, Landgren A, Landi MT, Li D, Liao Linda M, Malats N, McGlynn KA, McNeill LH, McWilliams RR, Melin BS, Mirabello L, Peplonska B, Peters U, Petersen GM, Prokunina-Olsson L, Purdue M, Qiao Y-L, Rabe KG, Rajaraman P, Real FX, Riboli E, Rodríguez-Santiago B, Rothman N, Ruder AM, Savage SA, Schwartz AG, Schwartz KL, Sesso HD, Severi G, Silverman DT, Spitz MR, Stevens VL, Stolzenberg-Solomon R, Stram D, Tang Z-Z, Taylor PR, Teras LR, Tobias GS, Viswanathan K, Wacholder S, Wang Z, Weinstein SJ, Wheeler W, White E, Wiencke JK, Wolpin BM, Wu X, Wunder JS, Yu K, Zanetti KA, Zeleniuch-Jacquotte A, Ziegler RG, de Andrade M, Barnes KC, Beaty TH, Bierut LJ, Desch KC, Doheny KF, Feenstra B, Ginsburg D, Heit JA, Kang JH, Laurie CA, Li JZ, Lowe WL, Marazita ML, Melbye M, Mirel DB, Murray JC, Nelson SC, Pasquale LR, Rice K, Wiggs JL, Wise A, Tucker M, Pérez-Jurado LA, Laurie CC, Caporaso NE, Yeager M, Chanock SJ (2015) Characterization of large structural genetic mosaicism in human autosomes. Am J Hum Genet 96(3):487–497. https://doi.org/10.1016/j.ajhg.2015.01.011 CrossRefPubMedPubMedCentral Machiela MJ, Zhou W, Sampson JN, Dean MC, Jacobs KB, Black A, Brinton LA, Chang IS, Chen C, Chen C, Chen K, Cook LS, Crous Bou M, De Vivo I, Doherty J, Friedenreich CM, Gaudet MM, Haiman CA, Hankinson SE, Hartge P, Henderson BE, Hong Y-C, Hosgood I HD III, Hsiung CA, Hu W, Hunter DJ, Jessop L, Kim HN, Kim YH, Kim YT, Klein R, Kraft P, Lan Q, Lin D, Liu J, Le Marchand L, Liang X, Lissowska J, Lu L, Magliocco AM, Matsuo K, Olson SH, Orlow I, Park JY, Pooler L, Prescott J, Rastogi R, Risch HA, Schumacher F, Seow A, Setiawan VW, Shen H, Sheng X, Shin M-H, Shu X-O, VanDen Berg D, Wang J-C, Wentzensen N, Wong MP, Wu C, Wu T, Wu Y-L, Xia L, Yang HP, Yang P-C, Zheng W, Zhou B, Abnet CC, Albanes D, Aldrich MC, Amos C, Amundadottir LT, Berndt SI, Blot WJ, Cathryn CH, Bracci PM, Burdett L, Buring JE, Butler MA, Carreón T, Chatterjee N, Chung CC, Cook MB, Cullen M, Davis FG, Ding T, Duell EJ, Epstein CG, Fan J-H, Figueroa JD, Fraumeni JF Jr., Freedman ND, Fuchs CS, Gao Y-T, Gapstur SM, Patiño-Garcia A, Garcia-Closas M, Gaziano JM, Giles GG, Gillanders EM, Giovannucci EL, Goldin L, Goldstein AM, Greene MH, Hallmans G, Harris CC, Henriksson R, Holly EA, Hoover RN, Hu N, Hutchinson A, Jenab M, Johansen C, Khaw K-T, Koh W-P, Laurence LN, Kooperberg C, Krogh V, Kurtz RC, LaCroix A, Landgren A, Landi MT, Li D, Liao Linda M, Malats N, McGlynn KA, McNeill LH, McWilliams RR, Melin BS, Mirabello L, Peplonska B, Peters U, Petersen GM, Prokunina-Olsson L, Purdue M, Qiao Y-L, Rabe KG, Rajaraman P, Real FX, Riboli E, Rodríguez-Santiago B, Rothman N, Ruder AM, Savage SA, Schwartz AG, Schwartz KL, Sesso HD, Severi G, Silverman DT, Spitz MR, Stevens VL, Stolzenberg-Solomon R, Stram D, Tang Z-Z, Taylor PR, Teras LR, Tobias GS, Viswanathan K, Wacholder S, Wang Z, Weinstein SJ, Wheeler W, White E, Wiencke JK, Wolpin BM, Wu X, Wunder JS, Yu K, Zanetti KA, Zeleniuch-Jacquotte A, Ziegler RG, de Andrade M, Barnes KC, Beaty TH, Bierut LJ, Desch KC, Doheny KF, Feenstra B, Ginsburg D, Heit JA, Kang JH, Laurie CA, Li JZ, Lowe WL, Marazita ML, Melbye M, Mirel DB, Murray JC, Nelson SC, Pasquale LR, Rice K, Wiggs JL, Wise A, Tucker M, Pérez-Jurado LA, Laurie CC, Caporaso NE, Yeager M, Chanock SJ (2015) Characterization of large structural genetic mosaicism in human autosomes. Am J Hum Genet 96(3):487–497. https://​doi.​org/​10.​1016/​j.​ajhg.​2015.​01.​011 CrossRefPubMedPubMedCentral
6.
go back to reference Bruder CEG, Piotrowski A, Gijsbers AACJ, Andersson R, Erickson S, Diaz de Ståhl T, Menzel U, Sandgren J, von Tell D, Poplawski A, Crowley M, Crasto C, Partridge EC, Tiwari H, Allison DB, Komorowski J, van Ommen G-JB, Boomsma DI, Pedersen NL, den Dunnen JT, Wirdefeldt K, Dumanski JP (2008) Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am J Hum Genet 82(3):763–771. https://doi.org/10.1016/j.ajhg.2007.12.011 CrossRefPubMedPubMedCentral Bruder CEG, Piotrowski A, Gijsbers AACJ, Andersson R, Erickson S, Diaz de Ståhl T, Menzel U, Sandgren J, von Tell D, Poplawski A, Crowley M, Crasto C, Partridge EC, Tiwari H, Allison DB, Komorowski J, van Ommen G-JB, Boomsma DI, Pedersen NL, den Dunnen JT, Wirdefeldt K, Dumanski JP (2008) Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am J Hum Genet 82(3):763–771. https://​doi.​org/​10.​1016/​j.​ajhg.​2007.​12.​011 CrossRefPubMedPubMedCentral
7.
go back to reference Hata A, Suzuki Y, Matsui I, Kuroki Y (1982) Ring 18 mosaicism in identical twins. Hum Genet 62(4):364–367CrossRef Hata A, Suzuki Y, Matsui I, Kuroki Y (1982) Ring 18 mosaicism in identical twins. Hum Genet 62(4):364–367CrossRef
8.
go back to reference Bourthoumieu S, Yardin C, Terro F, Gilbert B, Laroche C, Saura R, Vincent MC, Esclaire F (2005) Monozygotic twins concordant for blood karyotype, but phenotypically discordant: a case of “mosaic chimerism”. Am J Med Genet Part A 135(2):190–194CrossRef Bourthoumieu S, Yardin C, Terro F, Gilbert B, Laroche C, Saura R, Vincent MC, Esclaire F (2005) Monozygotic twins concordant for blood karyotype, but phenotypically discordant: a case of “mosaic chimerism”. Am J Med Genet Part A 135(2):190–194CrossRef
10.
go back to reference Baser ME, Friedman JM, Joe H, Shenton A, Wallace AJ, Ramsden RT, Evans DG (2011) Empirical development of improved diagnostic criteria for neurofibromatosis 2. Genet Med 13(6):576–581CrossRef Baser ME, Friedman JM, Joe H, Shenton A, Wallace AJ, Ramsden RT, Evans DG (2011) Empirical development of improved diagnostic criteria for neurofibromatosis 2. Genet Med 13(6):576–581CrossRef
Metadata
Title
Neurofibromatosis type 2 discordance in monozygous twins
Authors
S. Amico
P. Smith
S. Tobi
M. Perry
A. Wallace
D. G. Evans
Publication date
01-01-2020
Publisher
Springer Netherlands
Published in
Familial Cancer / Issue 1/2020
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-019-00148-2

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