RESUMO
AIMS: To identify the underlying mutations in our British families and sporadic patients with different types of corneal dystrophies (CDs) and to establish a phenotype-genotype correlation. METHODS: Twenty-nine patients, 9 sporadic and 20 patients from 7 families were subjected to both clinical and genetic examination. Slit lamp examination was performed for all patients who participated in the study to assess their corneal phenotype. Genomic DNA was extracted from 10 ml venous blood, and the BIGH3 gene was amplified exon by exon to perform heteroduplex analysis. Exons that displayed double bands were then analysed by direct bi-directional sequencing and restriction digest analyses. RESULTS: Clinically our patients showed three distinct phenotypes of CD: 16 with Thiel-Behnke corneal dystrophy or corneal dystrophy of Bowman layer type 2 (CDB2), 8 with granular CD (GCD), and 5 with lattice CD type I (LCDI). Three different missense mutations have been detected in the coding region of BIGH3 gene, R555Q, in 16 CDB2 patients, R555W in 8 GCD patients, and R124C in 5 LCDI patients. These mutations were the same as to those previously reported in patients from other ethnic origins. Also,we identified seven nucleotide substitutions that did not change the amino acid sequence of the encoded protein of which four were novel. CONCLUSIONS: In our patients of British origin, each phenotype of CD has been linked to a particular point mutation of the BIGH3 gene. Our study also highlights the importance of codons 124 and 555 as mutation hot spots in the BIGH3 gene in the British population.