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

Recent studies show that mutations in the gene encoding 11- cis retinol dehydrogenase are associated with fundus albipunctatus. The authors wanted to investigate whether additional, more severe, mutations in the 11- cis retinol dehydrogenase gene might be responsible for more severe forms of hereditary retinal diseases. Case-control molecular genetics study. Two index patients, 7 relatives, and 50 control individuals. The authors screened two index patients diagnosed with fundus albipunctatus for mutations in exons 2 to 5 and exon/intron boundaries of the 11- cis retinol dehydrogenase gene by direct sequencing. Control individuals were screened for the presence of the mutations using allele-specific oligonucleotide hybridization. Mutations in exons 2 to 5 and exon/intron boundaries of the 11- cis retinol dehydrogenase gene. 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 second 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. On the basis of our observations, it is unlikely that mutations in the 11- cis retinol dehydrogenase gene are associated with other, possibly more severe, retinal pathologic conditions/dystrophies or syndromic diseases in which the retina is also affected.