Surgical management and genetic analysis of a Chinese family with the S171P mutation in the UBIAD1 gene, the gene for Schnyder corneal dystrophy.

BACKGROUND: To describe the underlying molecular genetic basis, surgical management and phenotypic variation of Schnyder corneal dystrophy (SCD) identified in a four-generation Chinese family. METHODS: This is an interventional case series of 13 members from a non-consanguineous Chinese family. All patients underwent complete ophthalmological examination and slit-lamp photography. Subsequent corneal transplantations were performed (n = 3). Blood samples were taken for DNA extraction and subsequent genetic analysis. RESULTS: Genotyping indicated linkage to the locus at chromosome 1p36. Screening of the UBIAD1 gene identified a highly conserved mutation, Ser171Pro. Phenotypic variation in this large pedigree is similar to that seen in Caucasian patients. Surgical management of patients with anterior lamellar keratoplasty and deep anterior lamellar keratoplasty showed good visual outcomes. CONCLUSIONS: The S171P mutation is described for the first time in a Chinese family. This is the largest non-Caucasian pedigree described with SCD. Visual rehabilitation may be performed successfully with lamellar surgical procedures as opposed to full-thickness corneal grafts.

A human homolog of yeast pre-mRNA splicing gene, PRP31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11).

We report mutations in a gene (PRPF31) homologous to Saccharomyces cerevisiae pre-mRNA splicing gene PRP31 in families with autosomal dominant retinitis pigmentosa linked to chromosome 19q13.4 (RP11; MIM 600138). A positional cloning approach supported by bioinformatics identified PRPF31 comprising 14 exons and encoding a protein of 499 amino acids. The level of sequence identity to the yeast PRP31 gene indicates that PRPF31 is also likely to be involved in pre-mRNA splicing. Mutations that include missense substitutions, deletions, and insertions have been identified in four RP11-linked families and three sporadic RP cases. The identification of mutations in a pre-mRNA splicing gene implicates defects in the splicing process as a novel mechanism of photoreceptor degeneration.