Identification of a Genetic Mutation in a Family with Fructose-1,6-bisphosphatase Deficiency

Kikawa, Yoshiharu; Inuzuka, Manabu; Jin, Byun Young; Kaji, Satomi; Yamamoto, Yoshiki; Shigematsu, Yosuke; Nakai, Asami; Taketo, Akira; Ohura, Toshihiro; Mikami, Hitoshi; Mizunuma, Hideki; Suzuki, Yôichi; Narisawa, Kuniaki; Sudo, Masakatsu

doi:10.1006/bbrc.1995.1729

Cited by 27 publications

(21 citation statements)

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“…One mutation was a novel deletion of a single base “cytosine” (c.704delC) in exon 5, which resulted in a frameshift leading to a premature stop codon (p.Pro235GlnfsX42). The other was a hot-spot mutant site (c.960_961insG) in exon 7, leading to a premature stop codon (p.Ser321ValfsX13) [10]. Direct sequencing results confirmed the results and revealed that the patient’s father was heterozygous for the c.704delC mutation, and her mother was heterozygous for the c.960_961insG mutation, which means the genetic mutations in this pediatric patient were inherited from his parents (Figure 3A,B).…”

Section: Resultsmentioning

confidence: 65%

“…Since the first mutation was reported in 1995 [10], 35 different mutations have been reported, including 12 missense mutations, 12 deletion mutations, four nonsense mutations, four insertions/duplications, two splices, and one indel [13]. It has already been shown that next-generation sequencing is particularly suitable for the molecular diagnosis of complex metabolic disease [15].…”

Section: Discussionmentioning

confidence: 99%

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Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency

Niu

Chang

et al. 2017

IJMS

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Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare, autosomal recessive inherited disease caused by the mutation of the FBP1 gene, the incidence is estimated to be between 1/350,000 and 1/900,000. The symptoms of affected individuals are non-specific and are easily confused with other metabolic disorders. The present study describes the clinical features of four Chinese pediatric patients who presented with hypoglycemia, hyperlactacidemia, metabolic acidosis, and hyperuricemia. Targeted-next generation sequencing using the Agilent SureSelect XT Inherited Disease Panel was used to screen for causal variants in the genome, and the clinically-relevant variants were subsequently verified using Sanger sequencing. Here, DNA sequencing identified six variations of the FBP1 gene (NM_000507.3) in the four patients. In Case 1, we found a compound heterozygous mutations of c.704delC (p.Pro235GlnfsX42) (novel) and c.960_961insG (p.Ser321Valfs) (known pathogenic). In Case 2, we found a compound heterozygous mutations of c.825 + 1G>A and c.960_961insG (both were known pathogenically). In Case 3, a homozygous missense mutation of c.355G>A (p.Asp119Asn) (reported in ClinVar database without functional study) was found. Case 4 had a compound heterozygous mutations c.720_729del (p.Tyr241GlyfsX33) (novel) and c.490G>A (p.Gly164Ser) (known pathogenically). Further in vitro studies in the COS-7cell line demonstrated that the mutation of ASP119ASN had no impact on protein expression, but decreased the enzyme activity, and with which the clinical significance of Asp119Asn can be determined to be likely pathogenic. This report not only expands upon the known spectrum of variation of the FBP1 gene, but also deepens our understanding of the clinical features of FBPase deficiency.

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Section: Resultsmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency

Niu

Chang

et al. 2017

IJMS

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“…Other mutations, which have been described in FBP deficiency patients, encode for stop codons, frame shifts, missense changes, and exon 1 deletion [7,8,10,11,14]. The c. 117_118insACCTGC encoding for p.Cys39_Thr40dup is the only amino acid duplication that has been identified in FBP deficiency patients.…”

Section: Discussionmentioning

confidence: 96%

“…In another study, it was suggested that hypoglycemia in nine Arab patients was due to FBP deficiency [21]. Mutations in the FBP1 gene have been reported in Japanese, Asian, European, North American, and Moroccan patients [7,8,10,11,14,19], but not in Arab patients.…”

Section: Introductionmentioning

confidence: 98%

“…This disease is often fatal in the neonatal period and infancy. FBP deficiency is caused by mutations in the FBP1 gene, which encodes for fructose-1,6-bisphosphatase 1 (FBP1) [7,8,10,11,14,19]. FBP1 is a key regulator of gluconeogenesis, during which it catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate.…”

Section: Introductionmentioning

confidence: 99%

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