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European Journal of Pediatrics

, 168:1467 | Cite as

Novel FBP1 gene mutations in Arab patients with fructose-1,6-bisphosphatase deficiency

  • Muhammad Faiyaz-Ul-Haque
  • Mohammed Al-Owain
  • Fouad Al-Dayel
  • Zuhair Al-Hassnan
  • Hamad Al-Zaidan
  • Zuhair Rahbeeni
  • Moeen Al-Sayed
  • Ameera Balobaid
  • Ahmad Cluntun
  • Mohamed Toulimat
  • Hala Abalkhail
  • Iskra Peltekova
  • Syed H. E. Zaidi
Original Paper

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.

Conclusion

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.

Keywords

Autosomal recessive FBP1 gene Fructose-1,6-bisphosphatase deficiency Insertion mutation Nonsense mutation 

Abbreviations

FBP

Fructose-1,6-bisphosphatase

AMP

Adenosine monophosphate

AST

Aspartate transaminase

ALT

Alanine transaminase

Notes

Conflict of interest

Authors have no financial relationship with the organization that sponsored the research. There is no conflict of interest.

Supplementary material

431_2009_953_MOESM1_ESM.doc (28 kb)
Supplementary Table 1 Sequences of the primers employed. (DOC 27 kb)
431_2009_953_MOESM2_ESM.doc (38 kb)
Supplementary Table 2 Clinical details of the FBP deficient patients from family 1 of Arab ethnicity. (DOC 38 kb)

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Muhammad Faiyaz-Ul-Haque
    • 1
    • 2
  • Mohammed Al-Owain
    • 3
  • Fouad Al-Dayel
    • 1
  • Zuhair Al-Hassnan
    • 3
  • Hamad Al-Zaidan
    • 3
  • Zuhair Rahbeeni
    • 3
  • Moeen Al-Sayed
    • 3
  • Ameera Balobaid
    • 3
  • Ahmad Cluntun
    • 1
  • Mohamed Toulimat
    • 1
  • Hala Abalkhail
    • 1
  • Iskra Peltekova
    • 4
  • Syed H. E. Zaidi
    • 5
  1. 1.Molecular Genetics Laboratory, Department of Pathology & Laboratory MedicineKing Faisal Specialist Hospital & Research CentreRiyadhSaudi Arabia
  2. 2.College of MedicineAlfaisal UniversityRiyadhSaudi Arabia
  3. 3.Department of Medical GeneticsKing Faisal Specialist Hospital & Research CentreRiyadhSaudi Arabia
  4. 4.Department of MedicineQueen’s UniversityKingstonCanada
  5. 5.Department of MedicineUniversity Health Network and University of TorontoTorontoCanada

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