Abstract
BackgroundThe purpose of this study was to identify the genetic cause and describe the clinical phenotype of Schnyder corneal dystrophy (SCD) in six unrelated probands.MethodsWe 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.ResultsA 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.ConclusionAlthough 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.
Highlights
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
Schnyder corneal dystrophy (SCD; Mendelian Inheritance in Man (MIM) #121800) is a rare autosomal dominant disorder characterized by bilateral corneal opacification due to an accumulation of unesterified cholesterol and phospholipids in the corneal stroma [1]
SCD is caused by mutations in the UBIAD1 gene (MIM *611632), encoding a membrane-embedded UbiA prenyltransferase domain-containing protein which catalyses the Mg2+-dependent transfer of a hydrophobic polyprenyl chain onto a variety of acceptor molecules, including vitamin K and coenzyme Q [1, 4, 5]
Summary
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. Schnyder corneal dystrophy (SCD; MIM #121800) is a rare autosomal dominant disorder characterized by bilateral corneal opacification due to an accumulation of unesterified cholesterol and phospholipids in the corneal stroma [1]. SCD is caused by mutations in the UBIAD1 gene (MIM *611632), encoding a membrane-embedded UbiA prenyltransferase domain-containing protein which catalyses the Mg2+-dependent transfer of a hydrophobic polyprenyl chain onto a variety of acceptor molecules, including vitamin K and coenzyme Q [1, 4, 5]. At least 26 mutations that cause SCD have been identified to date [6]. In this study we report the clinical and genetic investigation of six probands of white and South Asian origin
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