R124C mutation of the βIGH3 gene leads to remarkable phenotypic variability in a Greek four-generation family with lattice corneal dystrophy type 1

Five autosomal dominantly inherited corneal dystrophies are caused by missense mutations in the βIGH3 gene on chromosome 5q31. Here we describe the clinical features and the analysis of the βIGH3 gene in a Greek four-generation family with lattice corneal dystrophy type 1 (CDL1). Sequencing of the βIGH3 cDNA from an affected family member revealed the R124C mutation. More recent data indicate that this is probably a mutation hot spot in CDL1. We could not find a common haplotype with another CDL1 family with the R124C mutation demonstrating that this mutation occurs independently in different families. The clinical course of the disease showed a remarkable variability between the affected family members. To investigate a possible role between the phenotypic variability and apolipoprotein E (ApoE), which co-localises with amyloid deposits in CDL1, we determined the ApoE genotype of all family members. The resulting data revealed no association with the variable clinical course.