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Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy

Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada.
PLoS ONE (Impact Factor: 3.53). 02/2007; 2(8):e685. DOI: 10.1371/journal.pone.0000685
Source: PubMed

ABSTRACT Schnyder crystalline corneal dystrophy (SCCD, MIM 121800) is a rare autosomal dominant disease characterized by progressive opacification of the cornea resulting from the local accumulation of lipids, and associated in some cases with systemic dyslipidemia. Although previous studies of the genetics of SCCD have localized the defective gene to a 1.58 Mbp interval on chromosome 1p, exhaustive sequencing of positional candidate genes has thus far failed to reveal causal mutations. We have ascertained a large multigenerational family in Nova Scotia affected with SCCD in which we have confirmed linkage to the same general area of chromosome 1. Intensive fine mapping in our family revealed a 1.3 Mbp candidate interval overlapping that previously reported. Sequencing of genes in our interval led to the identification of five putative causal mutations in gene UBIAD1, in our family as well as in four other small families of various geographic origins. UBIAD1 encodes a potential prenyltransferase, and is reported to interact physically with apolipoprotein E. UBIAD1 may play a direct role in intracellular cholesterol biochemistry, or may prenylate other proteins regulating cholesterol transport and storage.

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    • "G German–American c.890G>A G186R 2 2 [Weiss et al., 2008] EE Chinese–Taiwan c.897T>A L188H 2 2 [Nickerson et al., 2010] F118 Canadian c.1029A>G N232S 2 3 [Orr et al., 2007] "
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    Human Mutation 07/2013; 34(2). DOI:10.1002/humu.22230 · 5.05 Impact Factor
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    • "Mutations in the UBIAD1 gene are linked to the Schnyder Crystalline Corneal Syndrome (SCCD; OMIM 121800) (Weiss et al., 2007; Orr et al., 2007; Yellore et al., 2007). Two common UBIAD1 mutations found in SCCD patients lead to N102S and D112G substitutions. "
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    Cell 01/2013; 152(3):504-18. DOI:10.1016/j.cell.2013.01.013 · 33.12 Impact Factor
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    • "Overexpression of TERE1 in TCC cell line J82 alleviated the tumour phenotype, inhibiting the progression of cell cycle in cancer cells. Later, it was discovered that single copy loss of the TERE1 gene caused the dominant phenotype of SCCD (Orr et al., 2007). It was proposed by Fredericks et al. (2009) that the main function of TERE1 is to lower cholesterol inside the cell. "
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