title: The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe.
abstract: We investigated the molecular basis of hereditary fructose intolerance (HFI) in 80 patients from 72 families by means of a PCR-based mutation screening strategy, consisting of heteroduplex analysis, restriction enzyme digest, DNA single strand electrophoresis, and direct sequencing. For a subset of patients mutation screening with DHPLC was established which turned out to be as fast and as sensitive as the more conventional methods. Fifteen different mutations of the aldolase B (ALDOB) gene were identified in HFI patients. As in smaller previous studies, p.A150P (65%), p.A175D (11%) and p.N335K (8%) were the most common mutated alleles, followed by c.360_363delCAAA, p.R60X, p.Y204X, and c.865delC. Eight novel mutations were identified in eight families with HFI: a small indel mutation (c.1044_1049delTTCTGGinsACACT), two small deletions (c.345_372del28; c.841_842delAC), two splice site mutations (c.113-1G>A, c.799+2T>A), one nonsense mutation (c.612T>G (p.Y204X)), and two missense mutations (c.532T>C (p.C178R), c.851T>C (p.L284P)). By mutation screening for the three most common ALDOB mutations by DHPLC in 2,000 randomly selected newborns we detected 21 heterozygotes. Based on these data and after correction for less common and private ALDOB mutations, HFI prevalence in central Europe is estimated to be 1:26,100 (95% confidence interval 1: 12,600-79,000).
authors.affiliation: Dept. of Pediatrics, University Children's Hospital, Hamburg, Germany. r.santer@uke.uni-hamburg.de
authors.forename: René
authors.initials: R
authors.lastname: Santer
authors.forename: Johannes
authors.initials: J
authors.lastname: Rischewski
authors.forename: Michaela
authors.initials: M
authors.lastname: von Weihe
authors.forename: Marko
authors.initials: M
authors.lastname: Niederhaus
authors.forename: Sonja
authors.initials: S
authors.lastname: Schneppenheim
authors.forename: Kurt
authors.initials: K
authors.lastname: Baerlocher
authors.forename: Alfried
authors.initials: A
authors.lastname: Kohlschütter
authors.forename: Ania
authors.initials: A
authors.lastname: Muntau
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Posselt
authors.forename: Beat
authors.initials: B
authors.lastname: Steinmann
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneppenheim
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005060:Europe / Q000453:epidemiology; D005633:Fructose Intolerance / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation / Q000235:genetics*; D015997:Neonatal Screening; D015995:Prevalence
chemical_list: D005634:Fructose-Bisphosphate Aldolase