NULL ALLELES OF THE ALDOLASE-B GENE IN PATIENTS WITH HEREDITARY FRUCTOSE INTOLERANCE

We report three new mutations in the gene for aldolase B that are asso ciated with hereditary fructose intolerance (HFI). Two nonsense mutati ons create opal termination codons: R3op (C-->T, Arg(3)-->ter, exon 2) was found in homozygous form in four affected members of a large cons anguineous Turkish pedigree and R59op (C-->T, Arg(59)-->ter, exon 3) w as found on one allele in a woman of Austrian origin known to harbour one copy of the east European mutation, N334K (Asn(334)-->Lys). The th ird mutation occurred in a French HFI patient known to be heterozygous for the widespread mutation, A174D (Ala(174)-->Asp): a single mutatio n, G-->A, in the consensus acceptor site 3' of intron 6 was found on t he remaining allele. These mutations are predicted to abrogate synthes is of functional protein and thus represent null alleles of aldolase B . The mutant alleles can be readily detected in the amplification refr actory mutation system (ARMS) or (for R59op and 3' intron 6) by digest ion of amplified genomic fragments with DdeI or A1wNI, respectively, t o facilitate direct diagnosis of HFI by molecular analysis of aldolase B genes.