title: Novel FBP1 gene mutations in Arab patients with fructose-1,6-bisphosphatase deficiency.
abstract: Deficiency of fructose-1,6-bisphosphatase (FBP) results in impaired gluconeogenesis, which is characterized by episodes of hyperventilation, apnea, hypoglycemia, and metabolic and lactic acidosis. This autosomal recessive disorder is caused by mutations in the FBP1 gene, which encodes for fructose-1,6-bisphosphatase 1 (FBP1). Although FBP1 gene mutations have been described in FBP-deficient individuals of various ethnicities, there has been limited investigation into the genetics of this disorder in Arab patients. This study employed five consanguineous Arab families, in which 17 patients were clinically diagnosed with FBP deficiency. Seven patients and six carrier parents were analyzed for mutations in the FBP1 gene. DNA sequencing of the FBP1 gene identified two novel mutations in these families. A novel six nucleotide repetitive insertion, c114_119dupCTGCAC, was identified in patients from three families. This mutation encodes for a duplication of two amino acids (p.Cys39_Thr40dup) in the N-terminal domain of FBP1. A novel nonsense c.841G>T mutation encoding for a p.Glu281X truncation in the active site of FBP1 was discovered in patients from two families. The newly identified mutations in the FBP1 gene are predicted to produce FBP1 deficiency. These mutations are the only known genetic causes of FBP deficiency in Arab patients. The p.Cys39_Thr40dup is the first reported amino acid duplication in FBP deficiency patients.
  
  
  CONCLUSIONS
  This study provides a strong rationale for genetic testing of FBP deficient patients of Arab ethnicity for recurrent or novel mutations in the FBP1 gene.
authors.affiliation: Department of Pathology, Molecular Genetics Laboratory, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia. MFHaque@Kfshrc.edu.sa
authors.forename: Muhammad
authors.initials: M
authors.lastname: Faiyaz-Ul-Haque
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Owain
authors.forename: Fouad
authors.initials: F
authors.lastname: Al-Dayel
authors.forename: Zuhair
authors.initials: Z
authors.lastname: Al-Hassnan
authors.forename: Hamad
authors.initials: H
authors.lastname: Al-Zaidan
authors.forename: Zuhair
authors.initials: Z
authors.lastname: Rahbeeni
authors.forename: Moeen
authors.initials: M
authors.lastname: Al-Sayed
authors.forename: Ameera
authors.initials: A
authors.lastname: Balobaid
authors.forename: Ahmad
authors.initials: A
authors.lastname: Cluntun
authors.forename: Mohamed
authors.initials: M
authors.lastname: Toulimat
authors.forename: Hala
authors.initials: H
authors.lastname: Abalkhail
authors.forename: Iskra
authors.initials: I
authors.lastname: Peltekova
authors.forename: Syed H E
authors.initials: SH
authors.lastname: Zaidi
mesh_terms: D000328:Adult; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D015319:Fructose-1,6-Diphosphatase Deficiency / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D016254:Mutagenesis, Insertional; D009154:Mutation; D010375:Pedigree