title: Null alleles of the aldolase B gene in patients with hereditary fructose intolerance.
abstract: We report three new mutations in the gene for aldolase B that are associated with hereditary fructose intolerance (HFI). Two nonsense mutations create opal termination codons: R3op (C-->T, Arg3-->ter, exon 2) was found in homozygous form in four affected members of a large consanguineous Turkish pedigree and R59op (C-->T, Arg59-->ter, exon 3) was found on one allele in a woman of Austrian origin known to harbour one copy of the east European mutation, N334K (Asn334-->Lys). The third mutation occurred in a French HFI patient known to be heterozygous for the widespread mutation, A174D (Ala174-->Asp): a single mutation, G-->A, in the consensus acceptor site 3' of intron 6 was found on the remaining allele. These mutations are predicted to abrogate synthesis of functional protein and thus represent null alleles of aldolase B. The mutant alleles can be readily detected in the amplification refractory mutation system (ARMS) or (for R59op and 3' intron 6) by digestion of amplified genomic fragments with DdeI or A1wNI, respectively, to facilitate direct diagnosis of HFI by molecular analysis of aldolase B genes.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, UK.
authors.forename: M
authors.initials: M
authors.lastname: Ali
authors.forename: G
authors.initials: G
authors.lastname: Tunçman
authors.forename: N C
authors.initials: NC
authors.lastname: Cross
authors.forename: M
authors.initials: M
authors.lastname: Vidailhet
authors.forename: I
authors.initials: I
authors.lastname: Bökesoy
authors.forename: R
authors.initials: R
authors.lastname: Gitzelmann
authors.forename: T M
authors.initials: TM
authors.lastname: Cox
mesh_terms: D000483:Alleles; D001483:Base Sequence; D003241:Consanguinity; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D005633:Fructose Intolerance / Q000235:genetics*; D005634:Fructose-Bisphosphate Aldolase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D014421:Turkey
chemical_list: D017931:DNA Primers; D005634:Fructose-Bisphosphate Aldolase