May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Identification of a New Tgf-beta Family Member Associated With Ocular Anomalies
Author Affiliations & Notes
  • M. Ye
    Univ of Alberta, Edmonton, Alberta, Canada
    Ophthalmology,
  • M. Asai-coakwell
    Univ of Alberta, Edmonton, Alberta, Canada
    Ophthalmology,
  • C. French
    Univ of Alberta, Edmonton, Alberta, Canada
    Biological Sciences,
  • A. Waskiewicz
    Univ of Alberta, Edmonton, Alberta, Canada
    Biological Sciences,
  • O. Lehmann
    Univ of Alberta, Edmonton, Alberta, Canada
    Ophthalmology and Medical Genetics,
  • Footnotes
    Commercial Relationships  M. Ye, None; M. Asai-coakwell, None; C. French, None; A. Waskiewicz, None; O. Lehmann, None.
  • Footnotes
    Support  CIHR, AHFMR, CRC
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 447. doi:https://doi.org/
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    • Get Citation

      M. Ye, M. Asai-coakwell, C. French, A. Waskiewicz, O. Lehmann; Identification of a New Tgf-beta Family Member Associated With Ocular Anomalies. Invest. Ophthalmol. Vis. Sci. 2008;49(13):447. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : We previously demonstrated the role of one member of the BMP subfamily in causing microphthalmia /anophthalmia /coloboma (MAC) disorders. In view of the incompletely penetrant phenotypes observed in some pedigrees, we investigated whether other members of this large TGF-beta family might modulate, or contribute to, such phenotypes.

Methods: : To identify candidate genes, a large chromosomal anomaly database was first screened for patients with ocular phenotypes and segmental deletions encompassing TGF-beta family members. Subsequently, a small cohort of MAC patients was screened for mutations in a subset of these genes and in situ hybridization of 20-somite stage zebrafish performed to assess their expression pattern.

Results: : A heterozygous mutation in one TGF-beta family member was observed in 1 of 36 MAC patients, which was absent from 152 control individuals (p<0.05). This missense mutation replaces an evolutionary conserved amino acid with a cysteine. In situ hybridization of the zebrafish paralogue reveals ocular (and hindbrain) expression that is compatible with the patients’ unilateral iris and retino-choroidal coloboma phenotype.

Conclusions: : Our preliminary data have identified a single mutation in a little studied member of the TGF-beta family. Insertion of a cysteine is likely pathogenic due to cysteine’s known role in disulphide bond formation and ligand dimerization - indeed their numbers are so evolutionarily conserved that they form the basis of sub-classifying TGF-beta family members. Our ongoing studies include screening a larger panel of patients with MAC phenotypes for mutations in this gene and determining the effect of inhibiting its function with morpholino oligonucleotides.

Keywords: genetics • retinal development 
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