Hereditary fructose intolerance: frequency and spectrum mutations of the aldolase B gene in a large patients cohort from France--identification of eight new mutations.

Abstract

We investigated the molecular basis of hereditary fructose intolerance (HFI) in 160 patients from 92 families by means of a PCR-based mutation screening strategy, consisting of restriction enzyme digestion and direct sequencing. Sixteen different mutations of the aldolase B (ALDOB) gene were identified in HFI patients. As in previous studies, p.A150P (64%), p.A175D (16%) and p.N335K (5%) were the most common mutated alleles, followed by p.R60X, p.A338V, c.360_363delCAAA (p.N120KfsX30), c.324G>A (p.K108K) and c.625-1G>A. Eight novel mutations were also identified in 10 families with HFI: a one-base deletion (c.146delT (p.V49GfsX27)), a small deletion (c.953del42bp), a small insertion (c.689ins TGCTAA (p.K230MfsX136)), one splice site mutation (c.112+1G>A), one nonsense mutation (c.444G>A (p.W148X)), and three missense mutations (c.170G>C (p.R57P), c.839C>A (p.A280P) and c.932T>C (p.L311P)). Our strategy allows to diagnose 75% of HFI patients using restriction enzymatic analysis and to enlarge the diagnosis to 97% of HFI patients when associated with direct sequencing.

• Authors: Anne Davit-Spraul, Catherine Costa, Mokhtar Zater, Dalila Habes, Jacques Berthelot, Pierre Broué, François Feillet, Olivier Bernard, Philippe Labrune, Christiane Baussan
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 94 Issue 4 Pg. 443-447 (Aug 2008) ISSN: 1096-7206 [Electronic] United States
• PMID: 18541450 (Publication Type: Journal Article)

Chemical References

• Fructose-Bisphosphate Aldolase

Topics

• Adolescent
• Adult
• Child
• Child, Preschool
• Chromosomes, Human, Pair 9
• Cohort Studies
• DNA Mutational Analysis (methods)
• Female
• France
• Fructose Intolerance (enzymology, genetics)
• Fructose-Bisphosphate Aldolase (deficiency, genetics)
• Humans
• Infant
• Infant, Newborn
• Male
• Mutation