Skip to main content
SpringerLink
Log in

Winged Helix/Forkhead Transcription Factors and Rieger Syndrome

  • Chapter
The Molecular Mechanisms of Axenfeld-Rieger Syndrome

Part of the book series: Medical Intelligence Unit ((MIUN))

  • 386 Accesses

Abstract

A second locus for Rieger syndrome (RS) was identified from chromosomal abnormalities involving chromosome 6p25. Study of the breakpoint revealed mutations in the forkhead transcription factor (FOXC1) gene. Initially, this defect was identified in two patients with RS and glaucoma and later FOXC1 mutations were associated with RS patients. Several studies have shown linkage of anterior segment abnormalities to the same region of chromosome 6. These abnormalities include Axenfeld anomaly, Rieger anomaly, iridogoniodysgenesis anomaly and familial glaucoma iridogoniodysplasia. Axenfeld-Rieger syndrome (ARS) is a heterogeneous condition as noted by the identification of different chromosomal aberrations and phenotypes of ARS patients. This chapter will focus on the identification of FOXC1 and its association with the group of disorders that comprise Axenfeld-Rieger syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Mears AJ, Mirzayans F, Gould DB et al. Autosomal dominant iridogoniodysgenesis anomaly maps to 6p25. Am J Hum Genet 1996; 59(6):1321–1327.

    PubMed  CAS  Google Scholar 

  2. Mirzayans F, Mears AJ, Guo SW et al. Identification of the human chromosomal region containing the iridogoniodysgenesis anomaly locus by genomic-mismatch scanning. Am J Hum Genet 1997; 61(1):111–119.

    PubMed  CAS  Google Scholar 

  3. Gould DB, Mears AJ, Pearce WG et al. Autosomal dominant Axenfeld-Rieger anomaly maps to 6p25 [letter]. Am J Hum Genet 1997; 61(3):765–768.

    PubMed  CAS  Google Scholar 

  4. Jordan T, Ebenezer N, Manners R et al. Familial glaucoma iridogoniodysplasia maps to a 6p25 region implicated in primary congenital glaucoma and iridogoniodysgenesis anomaly. Am J Hum Genet 1997; 61(4):882–888.

    PubMed  CAS  Google Scholar 

  5. Morissette J, Falardeau P, Dubois S et al. A common gene for developmental and familial open-angle glaucomas confined on chromosome 6p25. Am J Hum Genet 1997; 61(4):A286.

    Google Scholar 

  6. Graff C, Jerndal T, Wadelius C. Fine mapping of the gene for autosomal dominant juvenile-onset glaucoma with iridogoniodysgenesis in 6p25-tel. Hum Genet 1997; 101(2):130–134.

    Article  PubMed  CAS  Google Scholar 

  7. Alward WL. Axenfeld-Rieger syndrome in the age of molecular genetics. Am J Ophthalmol 2000; 130(1):107–115.

    Article  PubMed  CAS  Google Scholar 

  8. Nishimura DY, Swiderski RE, Alward WL et al. The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25. Nat Genet 1998; 19(2):140–147.

    Article  PubMed  CAS  Google Scholar 

  9. Flomen RH, Vatcheva R, Gorman PA et al. Construction and analysis of a sequence-ready map in 4q25: Rieger syndrome can be caused by haploinsufficiency of RIEG, but also by chromosome breaks approximately 90 kb upstream of this gene. Genomics 1998; 47(3):409–413.

    Article  PubMed  CAS  Google Scholar 

  10. Mears AJ, Jordan T, Mirzayans F et al. Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly. Am J Hum Genet 1998; 63(5):1316–1328.

    Article  PubMed  CAS  Google Scholar 

  11. Kaestner KH, Knochel W, Martinez DE. Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev 2000; 14(2):142–146.

    PubMed  CAS  Google Scholar 

  12. Lai E, Prezioso VR, Tao WF et al. Hepatocyte nuclear factor 3 alpha belongs to a gene family in mammals that is homologous to the Drosophila homeotic gene fork head. Genes Dev 1991; 5(3):416–427.

    PubMed  CAS  Google Scholar 

  13. Weigel D, Jurgens G, Kuttner F et al. The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. Cell 1989; 57(4):645–658.

    Article  PubMed  CAS  Google Scholar 

  14. Kaufmann E, Knochel W. Five years on the wings of fork head. Mech Dev 1996; 57(1):3–20.

    Article  PubMed  CAS  Google Scholar 

  15. Pierrou S, Hellqvist M, Samuelsson L et al. Cloning and characterization of seven human forkhead proteins: Binding site specificity and DNA bending. EMBO J 1994; 13(20):5002–5012.

    PubMed  CAS  Google Scholar 

  16. Buchberger A, Schwarzer M, Brand T et al. Chicken winged-helix transcription factor cFKH-1 prefigures axial and appendicular skeletal structures during chicken embryogenesis. Dev Dyn 1998; 212(1):94–101.

    Article  PubMed  CAS  Google Scholar 

  17. Koster M, Dillinger K, Knochel W. Expression pattern of the winged helix factor XFD-11 during Xenopus embryogenesis. Mech Dev 1998; 76(1–2):169–173.

    Article  PubMed  CAS  Google Scholar 

  18. Topczewska JM, Topczewski J, Solnica-Krezel L et al. Sequence and expression of zebrafish foxcla and foxc1b, encoding conserved forkhead/winged helix transcription factors. Mech Dev 2001; 100(2):343–347.

    Article  PubMed  CAS  Google Scholar 

  19. Swiderski RE, Reiter RS, Nishimura DY et al. Expression of the Mf1 gene in developing mouse hearts: Implication in the development of human congenital heart defects. Dev Dyn 1999; 216(1):16–27.

    Article  PubMed  CAS  Google Scholar 

  20. Cunningham Jr ET, Eliott D, Miller NR et al. Familial Axenfeld-Rieger anomaly, atrial septal defect, and sensorineural hearing loss: A possible new genetic syndrome. Arch Ophthal 1998; 116(1):78–82.

    PubMed  Google Scholar 

  21. Baruch AC, Erickson RP. Axenfeld-Rieger anomaly, hypertelorism, dinodactyly, and cardiac anomalies in sibs with an unbalanced translocation der(6)t(6;8). Am J Med Genet 2001; 100(3):187–190.

    Article  PubMed  CAS  Google Scholar 

  22. Bekir NA, Gungor K. Atrial septal defect with interatrial aneurysm and Axenfeld-Rieger syndrome. Acta Ophthalmol Scand 2000; 78(1):101–103.

    Article  PubMed  CAS  Google Scholar 

  23. Mammi I, De Giorgio P, Clementi M et al. Cardiovascular anomaly in Rieger Syndrome: Heterogeneity or contiguity? Acta Ophthalmol Scand 1998; 76(4):509–512.

    Article  PubMed  CAS  Google Scholar 

  24. Mirzayans F, Gould DB, Heon E et al. Axenfeld-Rieger syndrome resulting from mutation of the FKHL7 gene on chromosome 6p25. Eur J Hum Genet 2000; 8(1):71–74.

    Article  PubMed  CAS  Google Scholar 

  25. Nishimura DY, Searby CC, Alward WL et al. A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye. Am J Hum Genet 2001; 68(2):364–372.

    Article  PubMed  CAS  Google Scholar 

  26. Suzuki T, Takahashi K, Kuwahara S et al. A novel (Pro79Thr) mutation in the FKHL7 gene in a Japanese family with Axenfeld-Rieger syndrome. Am J Ophthalmol 2001; 132(4):572–575.

    Article  PubMed  CAS  Google Scholar 

  27. Kawase C, Kawase K, Taniguchi T et al. Screening for mutations of Axenfeld-Rieger syndrome caused by FOXC1 gene in Japanese patients. J Glaucoma 2001; 10(6):477–482.

    Article  PubMed  CAS  Google Scholar 

  28. Borges AS, Susanna Jr R, Carani JC et al. Genetic analysis of PITX2 and FOXC1 in Rieger Syndrome patients from Brazil. J Glaucoma 2002; 11(1):51–56.

    Article  PubMed  Google Scholar 

  29. Lehmann OJ, Ebenezer ND, Ekong R et al. Ocular developmental abnormalities and glaucoma associated with interstitial 6p25 duplications and deletions. Invest Ophthalmol Vis Sci 2002; 43(6):1843–1849.

    PubMed  Google Scholar 

  30. Saleem RA, Banerjee-Basu S, Berry FB et al. Analyses of the effects that disease-causing missense mutations have on the structure and function of the winged-helix protein FOXC1. Am J Hum Genet 2001; 68(3):627–641.

    Article  PubMed  CAS  Google Scholar 

  31. Berry FB, Saleem RA, Walter MA. FOXC1 transcriptional regulation is mediated by N-and C-terminal activation domains and contains a phosphorylated transcriptional inhibitory domain. J Biol Chem 2002; 277(12):10292–10297.

    Article  PubMed  CAS  Google Scholar 

  32. Kume T, Deng KY, Winfrey V et al. The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation congenital hydrocephalus. Cell 1998; 93(6):985–996.

    Article  PubMed  CAS  Google Scholar 

  33. Hong HK, Lass JH, Chakravarti A. Pleiotropic skeletal and ocular phenotypes of the mouse mutation congenital hydrocephalus (ch/Mf1) arise from a winged helix/forkhead transcriptionfactor gene. Hum Mol Genet 1999; 8(4):625–637.

    Article  PubMed  CAS  Google Scholar 

  34. Kidson SH, Kume T, Deng K et al. The forkhead/winged-helix gene, Mf1, is necessary for the normal development of the cornea and formation of the anterior chamber in the mouse eye. Dev Biol 1999; 211(2):306–322.

    Article  PubMed  CAS  Google Scholar 

  35. Smith RS, Zabaleta A, Kume T et al. Haploinsufficiency of the transcription factors FOXC1 and FOXC2 results in aberrant ocular development. Hum Mol Genet 2000; 9(7):1021–1032.

    Article  PubMed  CAS  Google Scholar 

  36. Kume T, Deng K, Hogan BL. Murine forkhead/winged helix genes Foxcl (Mf1) and Foxc2 (Mfh1) are required for the early organogenesis of the kidney and urinary tract. Development 2000; 127(7):1387–1395.

    PubMed  CAS  Google Scholar 

  37. Kume T, Jiang H, Topczewska JM et al. The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis. Genes Dev 2001; 15(18):2470–2482.

    Article  PubMed  CAS  Google Scholar 

  38. Lehmann OJ, Ebenezer ND, Jordan T et al. Chromosomal duplication involving the forkhead transcription factor gene FOXC1 causes iris hypoplasia and glaucoma. Am J Hum Genet 2000; 67(5):1129–1135.

    PubMed  CAS  Google Scholar 

  39. Winnier GE, Kume T, Deng K et al. Roles for the winged helix transcription factors MF1 and MFH1 in cardiovascular development revealed by nonallelic noncomplementation of null alleles. Dev Biol 1999; 213(2):418–431.

    Article  PubMed  CAS  Google Scholar 

  40. Wang WH, McNatt LG, Shepard AR et al. Optimal procedure for extracting RNA from human ocular tissues and expression profiling of the congenital glaucoma gene FOXC1 using quantitative RT-PCR. Mol Vis 2001; 7:89–94.

    PubMed  CAS  Google Scholar 

  41. Stone EM, Fingert JH, Alward WLM et al. Identification of a gene that causes primary open angle glaucoma. Science 1997; 275(5300):668–670.

    Article  PubMed  CAS  Google Scholar 

  42. Swiderski RE, Ross JL, Fingert JH et al. Localization of MYOC transcripts in human eye and optic nerve by in situ hybridization. Invest Ophthalmol Vis Sci 2000; 41(11):3420–3428.

    PubMed  CAS  Google Scholar 

  43. Shields MB. Axenfeld-Rieger syndrome: A theory of mechanism and distinctions from the iridocorneal endothelial syndrome. Trans Am Ophthalmol Soc 1983; 81:736–784.

    PubMed  CAS  Google Scholar 

  44. Fang J, Dagenais SL, Erickson RP et al. Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. Am J Hum Genet 2000; 67(6):1382–1388.

    Article  PubMed  CAS  Google Scholar 

  45. Blixt A, Mahlapuu M, Aitola M et al. A forkhead gene, FoxE3, is essential for lens epithelial proliferation and closure of the lens vesicle. Genes Dev 2000; 14(2):245–254.

    PubMed  CAS  Google Scholar 

  46. Brownell I, Dirksen M, Jamrich M. Forkhead Foxe3 maps to the dysgenetic lens locus and is critical in lens development and differentiation. Genesis 2000; 27(2):81–93.

    Article  PubMed  CAS  Google Scholar 

  47. Semina EV, Brownell I, Mintz-Hittner HA et al. Mutations in the human forkhead transcription factor FOXE3 associated with anterior segment ocular dysgenesis and cataracts. Hum Mol Genet 2001; 10(3):231–236.

    Article  PubMed  CAS  Google Scholar 

  48. Ormestad M, Blixt A, Churchill A et al. Foxe3 haploinsufficiency in mice: A model for Peters’ anomaly. Invest Ophthalmol Vis Sci 2002; 43(5):1350–1357.

    PubMed  Google Scholar 

  49. Clark KL, Halay ED, Lai E et al. Cocrystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature 1993; 364(6436):412–420.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA

    Darryl Y. Nishimura & Ruth E. Swiderski

Authors
  1. Darryl Y. Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruth E. Swiderski
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Eurekah.com and Springer Science+Business Media

About this chapter

Cite this chapter

Nishimura, D.Y., Swiderski, R.E. (2005). Winged Helix/Forkhead Transcription Factors and Rieger Syndrome. In: The Molecular Mechanisms of Axenfeld-Rieger Syndrome. Medical Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-28672-1_2

Download citation

Publish with us

Policies and ethics

Search

Navigation