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. 2018 Sep 17;18(1):250.
doi: 10.1186/s12886-018-0918-8.

Schnyder Corneal Dystrophy and Associated Phenotypes Caused by Novel and Recurrent Mutations in the UBIAD1 Gene

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Free PMC article

Schnyder Corneal Dystrophy and Associated Phenotypes Caused by Novel and Recurrent Mutations in the UBIAD1 Gene

Cerys J Evans et al. BMC Ophthalmol. .
Free PMC article

Abstract

Background: The purpose of this study was to identify the genetic cause and describe the clinical phenotype of Schnyder corneal dystrophy (SCD) in six unrelated probands.

Methods: We identified two white Czech, two white British and two South Asian families with a clinical diagnosis of SCD. Ophthalmic assessment included spectral domain optical coherence tomography (SD-OCT) of one individual with advanced disease, and SD-OCT and confocal microscopy of a child with early stages of disease. UBIAD1 coding exons were amplified and Sanger sequenced in each proband. A fasting serum lipid profile was measured in three probands. Paternity testing was performed in one family.

Results: A novel heterozygous c.527G>A; p.(Gly176Glu) mutation in UBIAD1 was identified in one Czech proband. In the second Czech proband, aged 6 years when first examined, a previously described de novo heterozygous c.289G>A; p.(Ala97Thr) mutation was found. Two probands of South Asian descent carried a known c.305G>A; p.(Asn102Ser) mutation in the heterozygous state. Previously reported heterozygous c.361C>T; p.(Leu121Phe) and c.308C>T; p.(Thr103Ile) mutations were found in two white British families. Although crystalline deposits were present in all probands the affected area was small in some individuals. Corneal arcus and stromal haze were the most prominent phenotypical feature in two probands. In the Czech probands, SD-OCT confirmed accumulation of reflective material in the anterior stroma. Crystalline deposits were visualized by confocal microscopy. Mild dyslipidemia was found in all three individuals tested.

Conclusion: Although de novo occurrence of mutations in UBIAD1 is extremely rare, SCD should be considered in the differential diagnosis of bilateral corneal haze and/or crystal deposition, especially in children.

Keywords: Confocal microscopy; Crystalline deposits; De novo; Novel mutation; Schnyder corneal dystrophy; Spectral domain optical coherence tomography; UBIAD1.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Ethics committee of the General University Hospital in Prague (reference no. 151/11 S-IV) or Moorfields Eye Hospital (REC references 13/LO/1084 and 09/H0724/25). Written consent was obtained from all participants or their parents/legal guardians before inclusion.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Corneal phenotype observed in five probands with Schnyder corneal dystrophy. Ring of prominent superficial crystalline deposits in proband 1 aged 36 years (a), also documented by SD-OCT as a discontinuous hyper-reflective line beneath the epithelium and within the anterior corneal stroma (b). Discrete crystalline deposits in proband 2 aged 8 years (c) and more scattered opacities on SD-OCT (d). Central mid-stromal crystalline deposits in proband 3 aged 10 years (e). Diffuse stromal haze with prominent arcus in proband 4 aged 54 years (f, g) and proband 5 aged 37 years (h). Corneal crystals (arrows) were present in all probands, although in proband 2 they were a minor feature (b), corresponding to an early stage of the disease, and in probands 4 and 5 (g, h) they were present in only a very small area (arrows). All images show findings in the right eye
Fig. 2
Fig. 2
Corneal confocal microscopy imaging in an 8-year old child with Schnyder corneal dystrophy. Superficial epithelial cells with small round hyperreflective deposits (arrows) in the left eye (a). Normal appearance of the basal epithelial cell layer (b), and subepithelial nerve plexus in the right eye (c). Hyper-reflective deposits within and around keratocytes (arrows) (d) and needle-shaped crystals in anterior stroma of the left eye (e). Hyper-reflective deposits in mid-stroma in the left eye (f), but with unaffected posterior stroma (g) and endothelium in the left eye (h)
Fig. 3
Fig. 3
Pedigrees of the six families with Schnyder corneal dystrophy. Sequence electropherograms of the identified heterozygous mutations in UBIAD1 are also shown. The mutation arose de novo in family 2. Probands are indicated by an arrow and examined individuals by an asterisk. Mutation status in tested subjects is shown +/− for those who are heterozygous for a mutation in UBIAD1 and −/− for those who do not carry the pathogenic variant. Individuals known to be affected by Schnyder corneal dystrophy are shown in black, whereas a question mark indicates that the disease status of the individual was unknown

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