April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Discovery of A Novel UBIAD1 Mutation In A Swede Finn Pedigree With Schnyder Corneal Dystrophy Identified Two Decades Ago
Author Affiliations & Notes
  • Jayne S. Weiss
    Ophthalmology, Wayne State Univ/Kresge Eye Inst, Detroit, Michigan
  • Brittany Kostiha
    Cancer and Inflammation Program, NCI, NIH, Frederick, Maryland
  • Wolfgang Brandt
    Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Halle, Germany
  • Howard Kruth
    Division of Experimental Atherosclerosis, NHLBI,NIH, Bethesda, Maryland
  • Michael Dean
    National Cancer Institute, NCI,NIH, Frederick, Maryland
  • Mike Nickerson
    Cancer and Inflammation Program, NCI, NIH, Frederick, Maryland
  • Footnotes
    Commercial Relationships  Jayne S. Weiss, None; Brittany Kostiha, None; Wolfgang Brandt, None; Howard Kruth, None; Michael Dean, None; Mike Nickerson, None
  • Footnotes
    Support  Research to Prevent Blindness, Mid West Eye Banks
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1085. doi:
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      Jayne S. Weiss, Brittany Kostiha, Wolfgang Brandt, Howard Kruth, Michael Dean, Mike Nickerson; Discovery of A Novel UBIAD1 Mutation In A Swede Finn Pedigree With Schnyder Corneal Dystrophy Identified Two Decades Ago. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1085.

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

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Purpose: : Mutations in a novel gene, UBIAD1, were recently found to cause the autosomal dominant eye disease Schnyder corneal dystrophy (SCD). SCD is characterized by an abnormal deposition of cholesterol and phospholipids in the cornea resulting in progressive corneal opacification and visual loss. We characterized lesions in the UBIAD1 gene in a previously published Swede Finn SCD pedigree and examined protein homology, localization, and structure.

Methods: : SCD families were recruited and proband DNA was subject to genetic analysis by PCR and Sanger sequencing under IRB approved protocols. A novel alteration was detected in a SCD family which had been examined two decades ago. A different set of PCR primers, applied several years later, yielded a cosegregating mutation.

Results: : We characterized a single, novel DNA G>A change in the UBIAD1 gene that resulted in substitution of a conserved residue in a nonsynonymous fashion in a SCD pedigree that had been recruited two decades ago. Probands included members of this previously published SCD pedigree (Weiss JS.Cornea 11:93, 1992). Confounding issues with genetic analysis apparently prevented detection of the mutation using previously published assays. The alteration cosegregated with disease in 32 individuals, 17 affected and 15 unaffected, from four generations of this first family. Examination of protein homology revealed that amino acids altered in SCD were highly conserved across species. New and previously published SCD mutations were examined in a molecular model of the protein and revealed likely critical roles for SCD-mutant amino acids in protein structure and function. Potential primary and secondary substrate binding sites were identified and docking simulations indicated likely substrates including prenyl and phenolic molecules.

Conclusions: : Accumulating evidence from SCD familial mutations, protein homology across species, and molecular modeling suggest that protein function is likely down-regulated by SCD mutation. Mitochondrial UBIAD1 protein appears to have a highly conserved function that can be disrupted by an increasing number of mutations which cause disease. Treatment of disease based upon functional analysis of the gene and protein is discussed

Keywords: cornea: stroma and keratocytes • lipids • gene mapping 

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