April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Exclusion of pathogenic coding region mutations in the Xp22.3 locus associated with Lisch epithelial corneal dystrophy using next-generation sequencing
Author Affiliations & Notes
  • Doug Duk-Won Chung
    Cornea Division, Jules Stein Eye Institute, UCLA, Los Angeles, CA
  • Ricardo F Frausto
    Cornea Division, Jules Stein Eye Institute, UCLA, Los Angeles, CA
  • Anthony J Aldave
    Cornea Division, Jules Stein Eye Institute, UCLA, Los Angeles, CA
  • Footnotes
    Commercial Relationships Doug Chung, None; Ricardo Frausto, None; Anthony Aldave, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5521. doi:
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      Doug Duk-Won Chung, Ricardo F Frausto, Anthony J Aldave; Exclusion of pathogenic coding region mutations in the Xp22.3 locus associated with Lisch epithelial corneal dystrophy using next-generation sequencing. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5521.

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

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Abstract

Purpose: To determine the genetic basis of Lisch epithelial corneal dystrophy (LECD) using next-generation whole exome sequencing (WES).

Methods: Corneal slip-lamp examination and confocal microscopic imaging were performed to establish a diagnosis of LECD. Genomic DNA samples were collected and WES was performed using the Illumina HiSeq 2000 platform. Sequence reads were aligned using Partek Flow and the Bowtie 2 alignment algorithm. Variants were detected using SAMtools and filtered using the DNA-seq module in the Partek Genomics Suite software. Sequence reads with low quality scores were excluded. A list of genes containing novel or rare (MAF<0.05) non-synonymous variants in each of the LECD-affected probands was compiled.

Results: Slit-lamp examination demonstrated corneal features characteristic of LECD in four unrelated probands. Examination of the father of one of the probands revealed a LECD-like phenotype while the mother was unaffected. No genes in the LECD locus contained a novel or rare non-synonymous variant in each of the probands. Analysis of the remaining exome revealed 15 genes that contained rare or novel non-synonymous variants in each of the four probands.

Conclusions: Although a X-linked dominant inheritance pattern has been established for LECD in a previously-described family, we describe a probable father to son inheritance, consistent with an autosomal dominant mode of inheritance. This, in addition to the failure to identify a gene in the Xp22.3 locus containing a presumed pathogenic mutation in each of four affected probands, leads to the question of whether LECD could be an autosomal dominant disorder. We anticipate that WES of additional affected probands will narrow the list of potential candidate genes and lead to the identification of the genetic basis of LECD.

Keywords: 482 cornea: epithelium • 539 genetics • 494 degenerations/dystrophies  
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