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

Abstract

UNLABELLED:

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.

• Authors: 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
• Journal: European journal of pediatrics (Eur J Pediatr) Vol. 168 Issue 12 Pg. 1467-71 (Dec 2009) ISSN: 1432-1076 [Electronic] Germany
• PMID: 19259699 (Publication Type: Journal Article)

Topics

• Adult
• Consanguinity
• DNA Mutational Analysis
• Female
• Fructose-1,6-Diphosphatase Deficiency (ethnology, genetics)
• Humans
• Mutagenesis, Insertional
• Mutation
• Pedigree