Research Article Identification of the First De Novo UBIAD1 Gene Mutation Associated with Schnyder Corneal Dystrophy Benjamin R. Lin, Ricardo F. Frausto, Rosalind C. Vo, Stephan Y. Chiu, Judy L. Chen, and Anthony J. Aldave Stein Eye Institute, David Gefen School of Medicine at UCLA, 100 Stein Plaza, Los Angeles, CA 90095-7003, USA Correspondence should be addressed to Anthony J. Aldave; aldave@jsei.ucla.edu Received 24 January 2016; Revised 10 May 2016; Accepted 12 May 2016 Academic Editor: Vishal Jhanji Copyright © 2016 Benjamin R. Lin et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Purpose. To report the identiication of the irst de novo UBIAD1 missense mutation in an individual with Schnyder corneal dystrophy (SCD). Methods. A slit lamp examination was performed on a 47-year-old woman without a family history of corneal disorders. he proband’s parents, two sisters, and son were also examined and genomic DNA from all six individuals was collected. he exons and exon-intron boundaries of UBIAD1 were screened using Sanger sequencing. Identiied mutations were screened for in 200 control chromosomes. In silico analysis predicted the impact of identiied mutations on protein function and structure. Results. Slit lamp examination of the proband revealed indings consistent with SCD. Corneas of the family members appeared unafected. Screening of UBIAD1 in the proband identiied a novel heterozygous c.308C>T mutation, predicted to encode the missense amino acid substitution p.(hr103Ile). his mutation was not identiied in any of the family members or in 200 control chromosomes and was predicted to be damaging to normal protein function and structure. Conclusions. We present a novel heterozygous de novo missense mutation in UBIAD1, p.(hr103Ile), identiied in a patient with classic clinical features of SCD. his highlights the value of genetic testing in clinical diagnostic settings, even in the absence of a positive family history. 1. Introduction Schnyder corneal dystrophy (SCD; MIM #21800) was irst described by Van Went and Wibaut in 1924 and later by Schnyder in 1929 [1, 2]. Formerly known as Schnyder crystal- line corneal dystrophy or SCCD, it was subsequently renamed in 2008 by the International Committee for the Classiication of Corneal Dystrophies to SCD, as only about half of afected patients demonstrate corneal crystals on examination [3–5]. SCD is a rare autosomal dominant disorder associated with the development of central corneal stromal opaciication with or without subepithelial or anterior stromal crystalline deposi- tion in the irst or second decade of life [4, 6, 7]. Subsequently, afected individuals develop bilateral arcus lipoides and progressive stromal opaciication [4, 6, 7]. While SCD has been associated with systemic hyperlipi- demia, individuals with SCD have both normal and abnormal serum lipid, lipoprotein, and cholesterol levels, and Lisch and colleagues have found a lack of correlation between serum lipid levels and corneal indings [6, 8–14]. Nevertheless, a localized (i.e., corneal) dysregulation of lipid/cholesterol transport or aberrant lipid metabolism is thought to be a possible molecular cause of the SCD phenotype [6, 15]. In 1996, Shearman et al. performed genome-wide linkage analy- sis on two Scandinavian families with SCD and demonstrated linkage to a locus on chromosome 1 (1p.34.1–36) [16]. Eleven years later, Orr and colleagues and Weiss and colleagues inde- pendently identiied mutations in several highly conserved regions of the UbiA prenyltransferase domain containing 1 (UBIAD1) gene, located on chromosome 1p36 in eleven families [15, 17]. To date, a total of 25 mutations have been reported, but none were demonstrated to be spontaneous (Table 1). Herein, we report the irst conirmed de novo mutation associated with SCD. As such, we recommend that molecular genetic analysis be considered to conirm or refute a suspected clinical diagnosis of SCD, even in the setting of a negative family history. Hindawi Publishing Corporation Journal of Ophthalmology Volume 2016, Article ID 1968493, 9 pages http://dx.doi.org/10.1155/2016/1968493