title: Mutation analysis of the GLUT2 gene in three unrelated Egyptian families with Fanconi-Bickel syndrome: revisited gene atlas for renumbering.
abstract: BACKGROUND
  Fanconi-Bickel syndrome (FBS) is an autosomal recessive disorder caused by defects in the facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene which codes for the glucose transporter protein 2 expressed in hepatocytes and renal tubular cells causing a defect in carbohydrate metabolism, hepatomegaly, severe hypophosphatemic rickets and failure to thrive.
  
  
  METHODS
  Among 17 unrelated Egyptian families with heritable renal tubular acidosis, three families clinically suspected as FBS were enrolled for this study after providing written informed consent. The three families had positive consanguinity and index cases with characteristic clinical features of FBS (hepatorenal glycogen accumulation, glucose and galactose intolerance, fasting hypoglycemia, a characteristic tubular nephropathy). Laboratory work-up included urinalysis, renal and liver function tests, fasting and postprandial blood sugar, serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile and arterial blood gas analysis. Imaging studies included bone survey and abdominal ultrasound. Liver biopsy was performed to confirm pathological diagnosis of the liver enlargement. Molecular analysis was performed for all family members-polymerase chain reaction followed by direct sequencing of the coding segments as well as the flanking introns.
  
  
  RESULTS
  Three different mutations were detected, one specific for each family, including two new mutations. In the first family, exon 3, two bases (GA) were deleted (c.253_254delGA causing a frameshift mutation (p. Glu85fs); the patient presented with early symptoms but unfortunately died despite adequate treatment. In the second family, a mutation was found in exon 6, in the splicing acceptor site with intron 5 (c.776-1G>C or IVS5-1G>A). The third family showed a missense mutation C-to-T substitution at c.1250 (c.1250C>T) causing change of codon 417 (CCG) for proline to CTG for leucine (p. P417L); this is a well-known mutation in the Arab population previously localized in exon 9; however, it is currently renumbered to exon 10.
  
  
  CONCLUSIONS
  Neither the new mutations nor the reported one were particularly more frequent; however, the third mutation (c.1250C>T) needs more attention in survey studies especially if performed in Arab patients as it has been renumbered because of the 'change' of gene structure since the initial reports.
authors.affiliation: Department of Pediatrics, Genetics Unit, Mansoura University Children's Hospital (MUCH), 31 Bank Misr Street, Mansoura 35516, Egypt. m.alhaggar@yahoo.co.uk
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al-Haggar
authors.forename: Osamu
authors.initials: O
authors.lastname: Sakamoto
authors.forename: Ali
authors.initials: A
authors.lastname: Shaltout
authors.forename: Amani
authors.initials: A
authors.lastname: Al-Hawari
authors.forename: Yahya
authors.initials: Y
authors.lastname: Wahba
authors.forename: Dina
authors.initials: D
authors.lastname: Abdel-Hadi
mesh_terms: D018912:Arabs / Q000208:ethnology / Q000235:genetics*; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004534:Egypt; D005091:Exons / Q000235:genetics; D005198:Fanconi Syndrome / Q000208:ethnology / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D051273:Glucose Transporter Type 2 / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006529:Hepatomegaly / Q000473:pathology; D006801:Humans; D007223:Infant; D007438:Introns / Q000235:genetics; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*
chemical_list: D051273:Glucose Transporter Type 2