Mutations in Membrane Component, Chromosome 1, Surface Marker 1 (M1S1) gene in Gelatinous Drop–like Corneal Dystrophy

Abstract

Abstract: : Purpose: To report mutations in the membrane component, chromosome 1, surface marker 1 (M1S1) gene in a Japanese family with gelatinous drop–like corneal dystrophy (GDLD). Methods: This study had the approval of Juntendo University Hospital Ethics Committee and was conducted to conform to the tenets of the Declaration of Helsinki. Informed consent was obtained from the patients for molecular genetic study. Genomic DNA was extracted from leukocytes of peripheral blood of members of a GDLD family and controls, and the coding region of M1S1 was amplified by polymerase chain reaction (PCR). The PCR products were analyzed by direct sequencing. Normal and mutant M1S1 expression vectors were constructed and transfected into CHO cells to identify the cellular location of the gene products. Results: The affected members had compound heterozygous mutations consisting of a nonsense change at codon 84 (K84X) and a missense mutation resulting in a substitution of arginine by cysteine at codon108 (C108R). Neither of these mutations was found in the 50 controls. Protein expression analysis showed that C108R product was distributed diffusely in cytoplasm, whereas normal gene product accumulated at cell– cell adhesion borders. Conclusions: These data indicate that the K84X and C108R mutations in M1S1 cause GDLD.

Keywords: cornea: epithelium • genetics • cell adhesions/cell junctions