Identification Of Novel Mutations In Atypical Corneal Dystrophies By Genomic Analysis.

To describe the causal mutations in familial cases of atypical corneal dystrophies (ACD) defined as cases with a novel genotype, unexpected phenotype or different inheritance pattern from reported in literature.

Department of Genetics, Instituto de Oftalmología Conde de Valenciana, Mexico City.

Previous ophthalmological evaluation, cases underwent molecular analysis according to the inheritance pattern by Cornea and Genetics departments at Instituto de Oftalmología “Conde de Valenciana”. The Institutional Review Board and the ethics committee approved this study, which was performed in accordance with the tenets of the Declaration of Helsinki.

Six familial cases were included. First case was a unilateral lattice dystrophy with p.His626Arg mutation in TGFBI gene. Two cases of gelatinous dystrophy with inbreeding history, showed p.E111* and p.Leu235Ilefs*141 novel mutations in TACSTD2, respectively (first cases in Mexico) were treated with PK and KPRO. In a case with Thiel-Benhke dystrophy, a p.Arg555Gln change found in TGFBI helped for proper diagnosis and was managed with PTK. A novel heterozygous p.Met544Arg GSN mutation was found in a Meretoja’s syndrome. Other familial case of Fuch’s dystrophy suggested autosomal recessive pattern not previously described in literature but no mutation was identified.

This study set the molecular bases for 2 forms of ACD due to mutations in TGFBI, the description of 2 novel molecular changes for cases of gelatinous dystrophy and another for Meretoja’s syndrome in GSN. Preliminary results in the Fuchs’s case strengthen the possibility of a new gene for the disease.