A summary of molecular genetic findings in fructose-1,6-bisphosphatase deficiency with a focus on a common long-range deletion and the role of MLPA analysis

Abstract

BackgroundFructose-1,6-bisphosphatase deficiency is a rare inborn error of metabolism affecting gluconeogenesis with only sporadic reports on its molecular genetic basis.ResultsWe report our experience with mutation analysis in 14 patients (13 families) with fructose-1,6-bisphosphatase deficiency using conventional Sanger sequencing and multiplex ligation-dependent probe amplification analysis, and we provide a mutation update for the fructose bisphosphatase-1 gene (FBP1). Mutations were found on both chromosomes in all of our 14 patients including 5 novel mutations. Among the novel mutations is a 5412-bp deletion (c.-24-26_170 + 5192del) including the entire coding sequence of exon 2 of FBP1 that was repeatedly found in patients from Turkey and Armenia which may explain earlier poorly defined findings in patients from this area. This deletion can be detected with specific primers by generation of a junction fragment and by MLPA and SNP array assays. MLPA analysis was able to detect copy number variations in two further patients, one heterozygous for a deletion within exon 8, another heterozygous for a novel deletion of the entire FBP1 gene.ConclusionsBased on our update for the FBP1 gene, currently listing 35 mutations worldwide, and knowledge of PCR conditions that allow simple detection of a common FBP1 deletion in the Armenian and Turkish population, molecular genetic diagnosis has become easier in FBP1 deficiency. Furthermore, MLPA analysis may plays a useful role in patients with this disorder.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-016-0415-1) contains supplementary material, which is available to authorized users.

Targeting FBPase is an emerging novel approach for cancer therapy

“…Mutations in the FBP1 gene cause FBP1 deficiency, an inherited autosomal recessive disorder, which leads to the impairment of glucose synthesis from all gluconeogenic precursors [ 58 ]. This deficiency was first described by Baker and Winegrad in 1970 [ 59 ].…”

The essential role of fructose-1,6-bisphosphatase 2 enzyme in thermal homeostasis upon cold stress

“…In animal models, the inhibition of Fbp1 markedly inhibits gluconeogenesis and increases glucose sensitivity and utilization 12 . In humans, Fbp1 deficiency caused by Fbp1 mutations decreases gluconeogenesis 13 and leads to hypoglycemia, metabolic acidosis during fasting 14,15 , and unexpected infant death 16 . In contrast, the Fbp2 gene is expressed in nongluconeogenic organs and was identified in striated muscle by Krebs and Woodford in 1965 17 .…”

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“…Enzymatic defects manifest primarily as a deficiency of fructose-1,6-bisphosphatase (FBPase). Fructose-1,6-bisphosphatase deficiency is an autosomal, recessively inherited disease that progresses with severe hypoglycaemia and metabolic attacks resulting from the defect in gluconeogenesis [78][79][80]. Fructose-1,6-bisphosphatase deficiency was first described in 1970 [81].…”