LATTICE CORNEAL-DYSTROPHY TYPE-I - CLINIC AL AND MOLECULAR-GENETIC ANALYSIS IN A LARGE FAMILY

Background Lattice corneal dystrophy type I is one of the frequent for ms of stromal dystrophies following autosomal dominant inheritance. Th e beta-IG-h3 gene encoding keratoepithelin on the long arm of chromoso me 5 has recently been described as disease gene for lattice corneal d ystrophy type I as well as for three other corneal dystrophies with au tosomal dominant pattern of inheritance.Patients and methods Ten famil y members in three generations of a large family with autosomal domina nt lattice corneal dystrophy were analyzed clinically by slit-lamp bio microscopy. Mutation analysis in the beta-IG-h3 gene was carried out a t the mRNA level by RT-PCR and cDNA sequencing. Results A heterozygous single-base substitution (417C-->T) in exon 4 of the beta-IG-h3 gene was detected predicting the replacement of arginine-124 by cysteine. A nalysis of 10 family members showed perfect cosegregation of the mutat ion and lattice corneal dystrophy type I. The investigation excluded t his mutation in one family member previously classified as potentially affected. Conclusions The investigation confirmed autosomal dominant inheritance with complete penetrance in the family described. The muta tion 417C-->T has already been found earlier in another family of diff erent geographic origin. These results suggest a mutation hot spot at position 417. In addition, no evidence of genetic heterogeneity of lat tice corneal dystrophy type I was detected. Molecular genetic analysis tin conjunction with genetic counselling) therefore may be useful in routine diagnostics as the confirmation of the diagnosis by histologic al examination is possible only after keratoplasty. The common pathome chanism in lattice corneal dystrophy type I may facilitate development of new therapeutic concepts; the easy accessibility of the target org an may provide new possibilities e.g. for gene therapy.