title: Six novel alleles identified in Italian hereditary fructose intolerance patients enlarge the mutation spectrum of the aldolase B gene.
abstract: Hereditary fructose intolerance (HFI) is a recessively inherited disorder of carbohydrate metabolism caused by impaired functioning of human liver aldolase (B isoform; ALDOB). To-date, 29 enzyme-impairing mutations have been identified in the aldolase B gene. Here we report six novel HFI single nucleotide changes identified by sequence analysis in the aldolase B gene. Three of these are missense mutations (g.6846T>C, g.10236G>T, g.10258T>C), one is a nonsense mutation (g.8187C>T) and two affect splicing sites (g.8180G>C and g.10196A>G). We have expressed in bacterial cells the recombinant proteins corresponding to the g.6846T>C (p.I74T), g.10236G>T (p.V222F), and g.10258T>C (p.L229P) natural mutants to study their effect on aldolase B function and structure. All the new variants were insoluble; molecular graphics data suggest this is due to impaired folding.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico I, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Esposito
authors.forename: Rita
authors.initials: R
authors.lastname: Santamaria
authors.forename: Luigi
authors.initials: L
authors.lastname: Vitagliano
authors.forename: Luigi
authors.initials: L
authors.lastname: Ieno
authors.forename: Antonietta
authors.initials: A
authors.lastname: Viola
authors.forename: Laura
authors.initials: L
authors.lastname: Fiori
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Parenti
authors.forename: Lucia
authors.initials: L
authors.lastname: Zancan
authors.forename: Adriana
authors.initials: A
authors.lastname: Zagari
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005633:Fructose Intolerance / Q000201:enzymology / Q000235:genetics*; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D006801:Humans; D007558:Italy; D009154:Mutation
chemical_list: D005634:Fructose-Bisphosphate Aldolase