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.
BACKGROUND
Fructose-1,6-bisphosphatase deficiency is a rare inborn error of metabolism affecting gluconeogenesis with only sporadic reports on its molecular genetic basis.


RESULTS
We 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.


CONCLUSIONS
Based 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.
Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, D - 20246, Hamburg, Germany. r.santer@uke.de.
René
http://orcid.org/0000-0002-3670-5657
R
Santer
Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, D - 20246, Hamburg, Germany.
Marcel
M
du Moulin
Arabkir Institute of Child and Adolescent Health, Yerevan, Armenia.
Tatevik
T
Shahinyan
Institute of Human Genetics, University of Kiel, Kiel, Germany.
Inga
I
Vater
Department of Pediatrics, University Children's Hospital, Munich, Germany.
Esther
E
Maier
Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, D - 20246, Hamburg, Germany.
Ania C
AC
Muntau
Department of Pediatrics, University of Zurich, Zurich, Switzerland.
Beat
B
Steinmann
D056915:DNA Copy Number Variations / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D015319:Fructose-1,6-Diphosphatase Deficiency / Q000235:genetics*; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016601:RNA-Binding Proteins
D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; D016601:RNA-Binding Proteins; D004265:DNA Helicases
Armenia; FBP1 gene; Fructose bisphosphatase; MLPA; Turkey