MOLECULAR-BASIS HEREDITARY FRUCTOSE INTOLERANCE - MUTATIONS AND POLYMORPHISMS IN THE HUMAN ALDOLASE-B GENE

Mutations in the human aldolase B gene that result in hereditary fruct ose intolerance have been characterized extensively. Although the majo rity of subjects have been from northern Europe, subjects from other g eographical regions and ethnic groups have been identified. At present 21 mutations have been reported; 15 of these are single base substitu tions, resulting in nine amino acid replacements, four nonsense codons , and two putative splicing defects. Two large deletions, two four bas e deletions, a single-base deletion, and a seven base deletion/one bas e insertion have been found. This last mutation leads to a defect in s plicing and it is likely that one of the small deletions does as well. Regions of the enzyme where mutations have been observed recurrently are encoded by e?xons 5 and 9. Indeed, the three most common mutations are found in these exons. Two of these prevalent HFI mutations arose from a common ancestor and spread throughout the population by genetic drift. This finding was based on linkage to two sequence polymorphism s, which are among very few informative polymorphic markers that have been identified within the aldolase B gene. Because of the prevalence of a few HFI alleles, and the recent advances in molecular methods for identifying and screening for mutations, the diagnosis of HFI by mole cular screening methods should become routine, These molecular diagnos tic methods will be extremely beneficial for this often difficult to d iagnose and sometimes fatal disease. (C) 1995 Wiley-Liss, Inc.