title: The mutation spectrum of the facilitative glucose transporter gene SLC2A2 (GLUT2) in patients with Fanconi-Bickel syndrome.
abstract: We report a total of 23 novel mutations of the SLC2A2 ( GLUT2) gene in 49 patients with a clinical diagnosis of Fanconi-Bickel syndrome (FBS). Molecular genetic analysis has now been performed in more than 50% of the 109 FBS cases from 88 families that we have been able to locate world-wide since the original report in 1949. In these 49 patients, 33 different SLC2A2 mutations (9 missense, 7 nonsense, 10 frameshift, 7 splice-site) have been detected. Thus, our results confirm that mutations of SLC2A2 are the basic defect in patients with FBS. Mutations of SLC2A2 were detected in historical FBS patients in whom some of the characteristic clinical features (hepatorenal glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy) and the effect of therapy were described for the first time. Mutations were also found in patients with atypical clinical signs such as intestinal malabsorption, failure to thrive, the absence of hepatomegaly, or renal hyperfiltration. No single prevalent SLC2A2 mutation was responsible for a significant number of cases. In a high percentage (74%) of FBS patients, the mutation is homozygous, so we conclude that the prevalence of SLC2A2 mutations is relatively low in most populations. No mutational hot spots within SLC2A2 or even within homologous sequences among the genes for facilitative glucose transporters were detected.
authors.affiliation: Department of Pediatrics, University Children's Hospital, Schwanenweg 20, 24105 Kiel, Germany. santer@pediatrics.uni-kiel.de
authors.forename: René
authors.initials: R
authors.lastname: Santer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Groth
authors.forename: Martina
authors.initials: M
authors.lastname: Kinner
authors.forename: Anja
authors.initials: A
authors.lastname: Dombrowski
authors.forename: Gerard T
authors.initials: GT
authors.lastname: Berry
authors.forename: Johannes
authors.initials: J
authors.lastname: Brodehl
authors.forename: James V
authors.initials: JV
authors.lastname: Leonard
authors.forename: Shimon
authors.initials: S
authors.lastname: Moses
authors.forename: Svante
authors.initials: S
authors.lastname: Norgren
authors.forename: Flemming
authors.initials: F
authors.lastname: Skovby
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: Beat
authors.initials: B
authors.lastname: Steinmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schaub
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D002239:Carbohydrate Metabolism, Inborn Errors / Q000235:genetics*; D017931:DNA Primers; D016368:Frameshift Mutation; D051273:Glucose Transporter Type 2; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome
chemical_list: D017931:DNA Primers; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins