Method for determining eye disorders by determining mutations in 11-cis retinol dehydrogenase

Abstract

The invention relates to mutations in the gene encoding 11-cis retinal dehyrogenase. The mutations in the gene and in the resulting encoded protein are correlated to ocular disorders, such as fundus albipunctatus.

We claim:  
     
         1 . An isolated protein comprising the amino acid sequence of wild type retinol dehydrogenase as set forth in SEQ ID NO: 1, with the proviso that (i) amino acid 238 is not Gly or (ii) amino acid 73 is not Ser, or (iii) amino acid 33 is not Ile.  
     
     
         2 . The isolated protein of  claim 1  , wherein amino acid 238 is Trp rather than Gly.  
     
     
         3 . The isolated protein of  claim 1 , wherein amino acid 73 is Phe rather than Ser.  
     
     
         4 . The is olated protein of  claim 1 , wherein amino acid 33 is Val rather than Ile.  
     
     
         5 . An isolated nucleic acid molecule which encodes the protein of  claim 1 .  
     
     
         6 . An isolated nucleic acid molecule which encodes the protein of  claim 2 .  
     
     
         7 . An isolated nucleic acid molecule which encodes the protein of  claim 3 .  
     
     
         8 . An isolated nucleic acid molecule which encodes the protein of  claim 4 .  
     
     
         9 . Expression vector comprising the isolated nucleic acid molecule of  claim 5 , operably linked to a promoter.  
     
     
         10 . Recombinant cell comprising the isolated nucleic acid molecule of  claim 1 .  
     
     
         11 . Recombinant cell comprising the expression vector of  claim 9 .  
     
     
         12 . A method for determining possible presence of a disorder of the eye, comprising assaying a sample taken from a subject believed to have an eye disorder for a mutation in the nucleic acid molecule which encodes retinol dehydrogenase, presence of said mutation being indicative of possible presence of said disorder.  
     
     
         13 . The method of  claim 12 , said method comprising polymerase chain reaction.  
     
     
         14 . The method of  claim 12 , wherein said mutation is a mutation at the codon which encodes amino acid 73 of retinol dehydrogenase.  
     
     
         15 . The method of  claim 12 , wherein said mutation is a mutation at the codon which encodes amino acid 238 of retinol dehydrogenase.  
     
     
         16 . The method of  claim 15 , wherein said disorder is fundus albipunctatus.  
     
     
         17 . The method of  claim 16 , wherein said mutation occurs in both alleles of said subject's gene which encodes retinol dehydrogenase.  
     
     
         18 . The method of  claim 17 , wherein both of said alleles carry the same mutation.  
     
     
         19 . The method of  claim 17 , wherein each of said alleles carries a different mutation  
     
     
         20 . The method of  claim 18 , wherein said mutation results in a change from glycine to tryptophan at the codon for amino acid 238.  
     
     
         21 . The method of  claim 19 , wherein one of said alleles carries a mutation resulting in a change from glycine to tryptophan at the codon for amino acid 238, and the other allele carries a mutation resulting in a change at the codon for amino acid 73, resulting in a change from serine to phenylalanine.