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Genetics of Moyamoya Beyond RNF213: Monogenic Moyamoya Syndromes

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Moyamoya Disease Explored Through RNF213

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Abstract

Moyamoya angiopathy (MMA), in addition to its idiopathic form, so-called moyamoya disease (MMD), is also part of a broad spectrum of various diseases. In that situation, it is designated by the term moyamoya syndrome (MMS). Most MMS have a strong genetic component and include a heterogeneous group of monogenic disorders with highly variable clinical features and patterns of inheritance and penetrance. The recognition of known monogenic MMS entities and the delineation of novel ones are of major importance for disease prognosis, clinical care, accurate genetic counseling, gene identification, and MMA pathomechanisms understanding. In this chapter, we will focus on (i) RASopathies, a well-known group of Mendelian diseases whose gene identification established the role of the RAS/MAPK pathway in MMA, despite the low prevalence of MMA in those conditions and on (ii) some recently identified very rare Mendelian conditions with a highly penetrant MMA. We will also emphasize the importance of novel high-throughput methodologies to identify the genes involved in the numerous yet uncharacterized MMS.

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References

  1. Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med. 2009;360:1226–37.

    Article  CAS  PubMed  Google Scholar 

  2. Kuroda S, Houkin K. Moyamoya disease: current concepts and future perspectives. Lancet Neurol. 2008;7:1055–66.

    Article  Google Scholar 

  3. Kamada F, Aoki Y, Narisawa A, et al. A genome-wide association study identifies RNF213 as the first moyamoya disease gene. J Hum Genet. 2011;56(1):34–40.

    Article  CAS  PubMed  Google Scholar 

  4. Liu W, Morito D, Takashima S, Mineharu Y, Kobayashi H, Hitomi T, et al. Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development. PLoS One. 2011;6(7):e22542. doi:10.1371/journal.pone.0022542.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hayashi K, Horie N, Suyama K, Nagata I. An epidemiological survey of moyamoya disease, unilateral moyamoya disease and quasi-moyamoya disease in Japan. Clin Neurol Neurosurg. 2013;115(7):930–3.

    Article  PubMed  Google Scholar 

  6. Khan N, Schuknecht B, Boltshauser E, et al. Moyamoya disease and Moyamoya syndrome: experience in Europe; choice of revascularisation procedures. Acta Neurochir. 2003;145(12):1061–71.

    Article  CAS  PubMed  Google Scholar 

  7. Kraemer M, Heienbrok W, Berlit P. Moyamoya disease in Europeans. Stroke. 2008;39(12):3193–200.

    Article  PubMed  Google Scholar 

  8. Uchino K, Johnston SC, Becker KJ, Tirscwell DL. Moyamoya disease in Washington state and California. Neurology. 2005;65:956–8.

    Article  PubMed  Google Scholar 

  9. Mineharu Y, Liu W, Inoue K, et al. Autosomal dominant moyamoya disease maps to chromosome 17q25.3. Neurology. 2008;70:2357–63.

    Article  CAS  PubMed  Google Scholar 

  10. Guey S, Tournier-Lasserve E, Herve D, Kossorotoff M. Moyamoya disease and syndromes: from genetics to clinical management. Appl Clin Genet. 2015;8:49–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Tidyman WE, Rauen KA. The RASopathies: developmental syndrome of RAS/MAPK pathway dysregulation. Curr Opin Genet Dev. 2009;19:230–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol. 2014;13:834–43.

    Article  PubMed  Google Scholar 

  13. Cairns AG, North KN. Cerebrovascular dysplasia in neurofibromatosis type 1. J Neurol Neurosurg Psychiatry. 2008;79:1165–70.

    Article  CAS  PubMed  Google Scholar 

  14. Rosser TL, Vezina G, Packer RJ. Cerebrovascular abnormalities in a population of children with neurofibromatosis type 1. Neurology. 2005;64:553–5.

    Article  PubMed  Google Scholar 

  15. Sobata E, Ohkuma H, Suzuki S. Cerebrovascular disorders associated with von Recklinghausen’s neurofibromatosis: a case report. Neurosurgery. 1988;22:542–9.

    Google Scholar 

  16. Kaas B, Huisman TA, Tekes A, Bergner A, Blakeley JO, Jordan LC. Spectrum and prevalence of vasculopathy in pediatric neurofibromatosis type. J Child Neurol. 2013;28:561–9.

    Article  PubMed  Google Scholar 

  17. Koss MK, Scott M, Irons MB, Smith ER, Ullrich NJ. Moyamoya syndrome associated with neurofibromatosis type 1: perioperative and long-term outcome after surgical revascularization. J Neurosurg Pediatrics. 2013;11:417–25.

    Article  Google Scholar 

  18. Grill J, Couanet D, Cappelli C, Habrand JL, Rodriguez D, Sainte-Rose C, Kalifa C. Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma. Ann Neurol. 1999;45:393–6.

    Article  CAS  PubMed  Google Scholar 

  19. Phi JH, Choi JW, Seong MW, Kim T, Moon YJ, Lee J, et al. Association between Moyamoya syndrome and the RNF213 c.14576G>A variant in patients with neurofibromatosis type 1. J Neurosurg Pediatr. 2016 Feb;5:1–6.

    Google Scholar 

  20. Hamilton SJ, Friedman JM. Insights into the pathogenesis of neurofibromatosis 1 vasculopathy. Clin Genet. 2000;58:341–4.

    Article  CAS  PubMed  Google Scholar 

  21. Xu J, Ismat FA, Wang T, Yang J, Epstein JA. NF1 regulates a Ras-dependent vascular smooth muscle proliferative injury response. Circulation. 2007;116:2146–58.

    Google Scholar 

  22. Lasater EA, Li F, Bessler WK, Estes ML, Vemula S, Hingtgen CM, Dinauer MC, et al. Genetic and cellular evidence of vascular inflammation in neurofibromin-deficient mice and humans. J Clin Invest. 2010;120:859–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tartaglia M, Zampino G, Gelb BD. Noonan syndrome: clinical aspects and molecular pathogenesis. Mol Syndromol. 2010;1:2–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ganesan V, Kirkham FJ. Noonan syndrome and moyamoya. Pediatr Neurol apr. 1997;16(3):256–8.

    Article  CAS  Google Scholar 

  25. Schuster JM, Roberts TS. Symptomatic Moyamoya disease and aortic coarctation in a patient with Noonan’s syndrome. Pediatr Neurosurg. 1999;30:206–10.

    Article  CAS  PubMed  Google Scholar 

  26. Tang KT, Yang W, Wong J, Lee KY. Noonan syndrome associated with Moyamoya disease: report of one case. Acta Paediatr Taiwan. 1999;40:274–6.

    CAS  PubMed  Google Scholar 

  27. Yamashita Y, Kusaga A, Koga Y, Nagamitsu S, Matsuishi T. Noonan syndrome moyamoya-like vascular changes and antiphospholipid syndrome. Pediatr Neurol. 2004;31:364–6.

    Article  PubMed  Google Scholar 

  28. Gupta M, Choudhri OA, Feroze AH, Do HM, Gant GA, Steinberg GK. Management of moyamoya syndrome in patients with Noonan syndrome. J Clin Neurosci. 2016;28:107–11.

    Article  PubMed  Google Scholar 

  29. Mazzanti L, Cacciari E, Cicognani A, Bergamaschi R, Scarano E, Forabosco A. Noonan-like syndrome with loose anagen hair: a new syndrome. Am J Med Genet A. 2003;118A(3):279–86.

    Article  PubMed  Google Scholar 

  30. Cordeddu V, Di Schiavi E, Pennachio LA, Ma’ayan A, Sarkozy A, Fodale V, et al. Mutation in SHOC2 promotes aberrant protein N-myristoylation and underlies Noonan-like syndrome with loose anagen hair. Nat Genet. 2009;41:1022–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Choi JH, Oh MY, Yum MS, Lee BH, Kim GH, Yoo HW. Moyamoya syndrome in a patient with Noonan-like syndrome with loose anagen hair. Pediatr Neurol. 2015;52:352–5.

    Article  PubMed  Google Scholar 

  32. Lo FS, Wang CJ, Wong MC, Lee NC. Moyamoya disease in 2 patients with Noonan-like syndrome with loose anagen hair. Am J Med Genet Part A. 2015;167:1285.

    Article  CAS  PubMed  Google Scholar 

  33. Niemeyer CM, Kang MW, Shin DH, Furtan I, Erlacher M, Bunin NJ, et al. Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. Nat Genet. 2010;42:794–800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Martinelli S, De Luca A, Stellacci E, Rossi C, Checquolo S, Lepri F, et al. Heterozygous germline mutations in the CBL tumor suppressor gene cause a noonan syndrome-like phenotype. Am J Hum Genet. 2010;87:250–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Perez B, Mechinaud F, Galambrun C, Ben Romdhane N, Isidor B, Philip N, et al. Germline mutations of the CBL gene define a new genetic syndrome with predisposition to JMLL. J Med Genet. 2010;47:686–91.

    Article  CAS  PubMed  Google Scholar 

  36. Strullu M, Caya A, Cassinat B, Fenneteau O, Touzot F, Blauwblomme T, et al. In hematopoietic cells with a germline mutation of CBL, loss of heterozygosity is not a signature of juvenile myelo-monocytic leukemia. Leukemia. 2013;27:2404–7.

    Article  CAS  PubMed  Google Scholar 

  37. Yakuna M, Muramatsu H, Higa T, Chinen Y, Wang X, Kojima S. Germline mutation of CBL is associated with Moyamoya disease in a child with juvenile myelomonocytic leukemia and Noonan-like disorder. Pediatr Blood Cancer. 2015;62:542–4.

    Article  Google Scholar 

  38. Hervé D, Touraine P, Verloes A, Miskinyte S, Krivosic V, Logeart D, et al. A hereditary moyamoya syndrome with multisystemic manifestations. Neurology. 2010;75:259–64.

    Article  PubMed  Google Scholar 

  39. Miskinyte S, Butler MG, Hervé D, et al. Loss of BRCC3 deubiquitinating enzyme leads to abnormal angiogenesis and is associated with syndromic moyamoya. Am J Hum Genet. 2011;88(6):718–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Janczar S, Fogtman A, Koblowska M, Baranska D, Pastorczak A, Wegner O, et al. Novel severe hemophilia A and moyamoya (SHAM) syndrome caused by Xq28 deletions encompassing F8 and BRCC3 genes. Blood. 2014;123:4002–3.

    Article  CAS  PubMed  Google Scholar 

  41. Sowa ME, Bennett EJ, Gygi SP, Harper JW. Defining the human deubiquitinating enzyme interaction landscape. Cell. 2009;138:389–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Feng L, Wang J, Chen J. The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments. J Biol Chem. 2010;285:30982–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Yan K, Li L, Wang X, Hong R, Zhang Y, Yang H, Lin M, et al. The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells. J Cell Biol. 2015;210:209–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zheng H, Gupta V, Patterson-Fortin J, Bhattacharya S, Katlinski K, Wu J. A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon responses. Cell Rep. 2013;5(1):180–93.

    Article  CAS  PubMed  Google Scholar 

  45. Delaval B, Doxsey SJ. Pericentrin in cellular function and disease. J Cell Biol. 2010;188:181–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hitomi T, Habu T, Kobayashi H, Okuda H, Harada KH, Osafune K, et al. The moyamoya disease susceptibility variant RNF213 R4810K (rs112735431) induces genomic instability by mitotic abnormality. Biochem Biophys Res Commun. 2013;439:419–26.

    Article  CAS  PubMed  Google Scholar 

  47. Rodero MP, Crow YJ. Type I interferon-mediated monogenic autoinflammation : the type 1 interferonopathies, a conceptual overview. J Exp Med. 2016;7:1–12.

    Google Scholar 

  48. Hervé D, Philippi A, Belbouab R, et al. Loss of α1β1 soluble guanylate cyclase, the major nitric oxide receptor, leads to moyamoya and achalasia. Am J Hum Genet. 2014;94(3):385–94.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Bryan NS, Bian K, Murad F. Discovery of the nitric oxide pathway and targets for drug development. Front Biosci. 2009;14:1–18.

    Article  CAS  Google Scholar 

  50. Wallace S, Guo DC, Regalado E, Mellor-Crumley L, Banshad M, Nickerson D, et al. Disrupted nitric oxide signaling due to GUCY1A3 mutations increases risk for moyamoya disease, achalasia and hypertension. Clin Genet. 2016;90:351–60.

    Article  CAS  PubMed  Google Scholar 

  51. Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461:272–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Inserm UMR-S1161, Université Paris 7 Denis Diderot, Sorbonne Paris Cité, Paris, France

    S. Guey, L. Grangeon, F. Riant & D. Hervé

  2. Department of Neurology, Alfried-Krupp-Hospital Essen, Essen, Germany

    M. Kraemer

  3. AP-HP, Groupe hospitalier Lariboisière-Saint-Louis, Service de génétique neurovasculaire, and Centre de Référence des maladies Vasculaires Rares du Cerveau et de l’Œil (CERVCO), 75010, Paris, France

    F. Riant

  4. AP-HP, French Center for Pediatric Stroke and Pediatric Neurology Department, University Hospital Necker-Enfants malades, Paris, France

    M. Kossorotoff

  5. AP-HP, Groupe Hospitalier Saint-Louis Lariboisière, Service de Neurologie, and Centre de Référence des maladies Vasculaires Rares du Cerveau et de l’Œil (CERVCO), 75010, Paris, France

    D. Hervé

  6. CHU Paris‐GH St‐Louis Lariboisière F‐Widal, Hôpital Lariboisière, Paris, France

    E. Tournier-Lasserve

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  1. S. Guey
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  2. M. Kraemer
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  3. L. Grangeon
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  4. F. Riant
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  5. M. Kossorotoff
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  6. D. Hervé
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  7. E. Tournier-Lasserve
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Corresponding author

Correspondence to E. Tournier-Lasserve .

Editor information

Editors and Affiliations

  1. Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Akio Koizumi

  2. Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan

    Kazuhiro Nagata

  3. Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Kiyohiro Houkin

  4. Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan

    Teiji Tominaga

  5. Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Susumu Miyamoto

  6. Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan

    Shigeo Kure

  7. CHU Paris‐GH St‐Louis Lariboisière F‐Widal, Hôpital Lariboisière, Paris, France

    Elizabeth Tournier-Lasserve

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Guey, S. et al. (2017). Genetics of Moyamoya Beyond RNF213: Monogenic Moyamoya Syndromes. In: Koizumi, A., et al. Moyamoya Disease Explored Through RNF213. Current Topics in Environmental Health and Preventive Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-10-2711-6_9

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  • DOI: https://doi.org/10.1007/978-981-10-2711-6_9

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  • Online ISBN: 978-981-10-2711-6

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