title: Hereditary fructose intolerance: functional study of two novel ALDOB natural variants and characterization of a partial gene deletion.
abstract: Hereditary fructose intolerance (HFI) is an autosomal recessive metabolic disease caused by impaired functioning of human liver aldolase (ALDOB). At least 54 subtle/point mutations and only two large intragenic deletions have been found in the ALDOB gene. Here we report two novel ALDOB variants (p.R46W and p.Y343H) and an intragenic deletion that we found in patients with suspected HFI. The residual catalytic activity of the recombinant p.R46W and p.Y343H variants toward F1P was particularly altered. We also characterized a large intragenic deletion that we found in six unrelated patients. This is the first report of six unrelated patients sharing the same ALDOB deletion, thus indicating a founder effect for this allele in our geographic area. Because this deletion involves ALDOB exon 5, it can mimic worldwide common pathogenic genotypes, that is, homozygous p.A150P and p.A175D. Finally, the identification of only one ALDOB mutation in symptomatic patients suggests that HFI symptoms can, albeit rarely, appear also in heterozygotes. Therefore, an excessive and continuous fructose dietary intake may have deleterious effects even in apparently asymptomatic HFI carriers.
authors.affiliation: CEINGE-Biotecnologie Avanzate S.C.a r.l., Napoli, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Esposito
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Imperato
authors.forename: Luigi
authors.initials: L
authors.lastname: Ieno
authors.forename: Rosa
authors.initials: R
authors.lastname: Sorvillo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Benigno
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Parenti
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.forename: Luigi
authors.initials: L
authors.lastname: Vitagliano
authors.forename: Adriana
authors.initials: A
authors.lastname: Zagari
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002648:Child; D002942:Circular Dichroism; D017809:Fatal Outcome; D005260:Female; D005633:Fructose Intolerance / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry / Q000235:genetics*; D017353:Gene Deletion; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D007223:Infant; D007558:Italy; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D005634:Fructose-Bisphosphate Aldolase