Advertisement

Genetic Linkage Study

  • Shigeo Kure

Abstract

Ikeda et al. performed a genome-wide linkage study using 16 Japanese families with moyamoya disease and 371 microsatellite markers [1]. In the study 13 of 16 families had sibling cases and the rest of them included parent—children transmission of the disease. Maximum nonparametric linkage (NPL) score of 3.4 was found at the marker D3S3050. NPL score of greater than 3.0 was observed at the three microsatellite markers, D3S2387, D3S3050, and D3S1560, which are located on chromosome 3p24.2-p26 (Fig. 1). In moyamoya disease, abnormal vascular formation is observed mainly in brain. Marfan syndrome is an extracellular matrix disorder with cardinal manifestations in the cardiovascular and skeleton systems. Moyamoya-like angiographic findings are sometimes associated with Marfan syndrome. Most patients with Marfan syndrome have mutations in fibrillin gene (FRN) on chromosome 15q21 [2]. The second locus for Marfan syndrome has been mapped at chromosome 3p25-24.2 [3]. Recently, TGFBR2, a putative tumor-suppressor gene implicated in several malignancies, has been identified for the second gene for Marfan syndrome [4]. Mutational analysis of TGFBR2 in patients with moyamoya disease has not been reported. Yamamoto et al. hypothesized that paternally imprinted gene might be associated with this disorder because of a high incidence of maternal inheritance in familial moyamoya disease. Although they screened genes with monoallelic expressions on chromosome 3, no imprinting gene was identified in this region [5].

Keywords

Human Leukocyte Antigen Human Leukocyte Antigen Class Marfan Syndrome Moyamoya Disease Human Leukocyte Antigen Allele 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Ikeda H, Sasaki T, Yoshimoto T et al (1999) Mapping of a familial moyamoya disease gene to chromosome 3p24.2-p26. Am J Hum Genet 64:533–537PubMedCrossRefGoogle Scholar
  2. 2.
    Dietz HC, Cutting GR, Pyeritz RE et al (1991) Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 352:337–339PubMedCrossRefGoogle Scholar
  3. 3.
    Collod G, Babron MC, Jondeau G et al (1994) A second locus for Marfan syndrome maps to chromosome 3p24.2-p25. Nat Genet 8:264–268PubMedCrossRefGoogle Scholar
  4. 4.
    Mizuguchi T, Collod-Beroud G, Akiyama T et al (2004) Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet 36:855–860PubMedCrossRefGoogle Scholar
  5. 5.
    Yamamoto T, Akasaka Y, Ohtani K et al (2005) Molecular screening for moyamoya disease by use of expressed sequence tag on chromosome 3p. No To Hattatsu 37:20–25PubMedGoogle Scholar
  6. 6.
    Aoyagi M, Ogami K, Matsushima Y et al (1995) Human leukocyte antigen in patients with moyamoya disease. Stroke 26:415–417PubMedCrossRefGoogle Scholar
  7. 7.
    Inoue TK, Ikezaki K, Sasazuki T et al (1997) DNA typing of HLA in the patients with moyamoya disease. Jpn J Hum Genet 42:507–515PubMedCrossRefGoogle Scholar
  8. 8.
    Inoue TK, Ikezaki K, Sasazuki T et al (2000) Linkage analysis of moyamoya disease on chromosome 6. J Child Neurol 15:179–182PubMedCrossRefGoogle Scholar
  9. 9.
    Han H, Pyo CW, Yoo DS et al (2003) Associations of moyamoya patients with HLA class I and class II alleles in the Korean population. J Korean Med Sci 18:876–880PubMedGoogle Scholar
  10. 10.
    Sakurai K, Horiuchi Y, Ikeda H et al (2004) A novel susceptibility locus for moyamoya disease on chromosome 8q23. J Hum Genet 49:278–281PubMedCrossRefGoogle Scholar
  11. 11.
    Yamamoto M, Aoyagi M, Fukai N et al (1998) Differences in cellular responses to mitogens in arterial smooth muscle cells derived from patients with moyamoya disease. Stroke 29:1188–1193PubMedCrossRefGoogle Scholar
  12. 12.
    Hojo M, Hoshimaru M, Miyamoto S et al (1998) Role of transforming growth factor-beta1 in the pathogenesis of moyamoya disease. J Neurosurg 89:623–629PubMedCrossRefGoogle Scholar
  13. 13.
    Yamauchi T, Tada M, Houkin K et al (2000) Linkage of familial moyamoya disease (spontaneous occlusion of the circle of Willis) to chromosome 17q25. Stroke 31:930–935PubMedCrossRefGoogle Scholar
  14. 14.
    Nanba R, Tada M, Kuroda S (2005) Sequence analysis and bioinformatics analysis of chromosome 17q25 in familial moyamoya disease. Childs Nerv Syst 21:62–68PubMedCrossRefGoogle Scholar
  15. 15.
    Kang HS, Kim SK, Cho BK et al (2006) Single nucleotide polymorphisms of tissue inhibitor of metal-loproteinase genes in familial moyamoya disease. Neurosurgery 58:1074–1080; discussion-80PubMedCrossRefGoogle Scholar
  16. 16.
    Johnson C, Galis ZS (2004) Matrix metalloproteinase-2 and -9 differentially regulate smooth muscle cell migration and cell-mediated collagen organization. Arterioscler Thromb Vasc Biol 24:54–60PubMedCrossRefGoogle Scholar
  17. 17.
    Mineharu Y, Liu W, Inoue K et al (2008) Autosomal dominant moyamoya disease maps to chromosome 17q25.3. Neurology 70:2357–2363PubMedCrossRefGoogle Scholar
  18. 18.
    Shiratsuchi T, Oda K, Nishimori H et al (1998) Cloning and characterization of BAP3 (BAI-associated protein 3), a C2 domain-containing protein that interacts with BAI1. Biochem Biophys Res Commun 251:158–165PubMedCrossRefGoogle Scholar
  19. 19.
    Meschia JF, Ross OA (2008) Heterogeneity of moyamoya disease:after a decade of linkage, is there new hope for a gene? Neurology 70:2353–2354PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2010

Authors and Affiliations

  • Shigeo Kure
    • 1
  1. 1.Department of PediatricsTohoku University School of Medicine, SeiryomachiAobakuJapan

Personalised recommendations