Null mutation in the human 11-cis retinol dehydrogenase gene associated with fundus albipunctatus

Purpose: Recent studies show that mutations in the gene encoding 11-cis ret inol dehydrogenase are associated with fundus albipunctatus. The authors wa nted to investigate whether additional, more severe, mutations in the 11-ci s retinol dehydrogenase gene might be responsible for more severe forms of hereditary retinal diseases. Design: Case-control molecular genetics study. Participants and Controls: Two index patients, 7 relatives, and 50 control individuals. Methods: The authors screened two index patients diagnosed with fundus albi punctatus for mutations in exons 2 to 5 and exon/intron boundaries of the 1 1-cis retinol dehydrogenase gene by direct sequencing. Control individuals were screened for the presence of the mutations using allele-specific oligo nucleotide hybridization. Main Outcome Measures: Mutations in exons 2 to 5 and exon/intron boundaries of the 11-cis retinol dehydrogenase gene. Results: In a compound heterozygote, two novel mutations were found: a 4 bp insertion in exon 2 and a missense mutation Cys267Trp in exon 5. In a seco nd pedigree, a homozygous frameshift mutation in codon 43 (Arg42ct[1-bpdel] ) was detected. In both families, the mutations segregate with the disease. The mutations were not found in 50 control individuals. Conclusions: On the basis of our observations, it is unlikely that mutation s in the 11-cis retinol dehydrogenase gene are associated with other, possi bly more severe, retinal pathologic conditions/dystrophies or syndromic dis eases in which the retina is also affected. Ophthalmology 2001;108:1479-148 4 (C) 2001 by the American Academy of Ophthalmology.