Identification of a Novel UBIAD1 Mutation in a Chinese Family With Schnyder Crystalline Corneal Dystrophy (SCCD)

Abstract

Purpose: : Schnyder crystalline corneal dystrophy (SCCD) is a rare autosomal dominant disease characterized by abnormal increase in cholesterol and phospholipids deposition in the cornea. A genome wide linkage analysis in Swede-Finn pedigrees mapped the SCCD locus to chromosome 1p36. The SCCD gene at this locus was recently identified as UBIAD1. The aim of our work was to identify the molecular genetic basis of disease in a non-consanguineous four-generation Chinese Singaporean family with bilateral corneal abnormalities characteristic of SCCD.

Methods: : The Chinese SCCD family was subjected to a complete ophthalmic examination that included slit-lamp examination and slit lamp photography to assess and document the crystalline deposits and arcus lipoides. Blood samples were taken for subsequent genetic analysis. Ten microsatellite markers from the SCCD locus at chromosome 1p36 were genotyped using an ABI 3100 Genetic Analyzer. Two-point and multipoint LOD scores were calculated using the MLINK option of the Cyrillic pedigree information package. The 2 coding exons of the UBIAD1 gene were screened for mutations by direct sequencing.

Results: : The Chinese SCCD family was confirmed to be linked to the known SCCD locus with a maximum two-point LOD score of 2.13 at theta=0.00 with marker D1S244. Screening of UBIAD1 gene in the Chinese SCCD1 family, identified a novel mutation at position c.511T>C that leads to a substitution of serine by proline at codon 171 (p.Ser171Pro). The Ser171 amino acid residue is highly conserved in mammalian, avian and insect homologs of UBIAD1 protein. All affected individuals were heterozygous for the c.511T>C transition mutation that was absent in >180 control Chinese chromosomes indicating p.Ser171Pro to be the disease causative mutation in this family.

Conclusions: : Identification of a novel UBIAD1 mutation in the first ever Chinese family to be reported with SCCD indicates that SCCD is likely to be genetically homogeneous.

Keywords: genetics