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

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 metabol...

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Autores principales: Li, Niu, Chang, Guoying, Xu, Yufei, Ding, Yu, Li, Guoqiang, Yu, Tingting, Qing, Yanrong, Li, Juan, Shen, Yiping, Wang, Jian, Wang, Xiumin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412439/
https://www.ncbi.nlm.nih.gov/pubmed/28420223
http://dx.doi.org/10.3390/ijms18040857
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author Li, Niu
Chang, Guoying
Xu, Yufei
Ding, Yu
Li, Guoqiang
Yu, Tingting
Qing, Yanrong
Li, Juan
Shen, Yiping
Wang, Jian
Wang, Xiumin
author_facet Li, Niu
Chang, Guoying
Xu, Yufei
Ding, Yu
Li, Guoqiang
Yu, Tingting
Qing, Yanrong
Li, Juan
Shen, Yiping
Wang, Jian
Wang, Xiumin
author_sort Li, Niu
collection PubMed
description 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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spelling pubmed-54124392017-05-05 Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency Li, Niu Chang, Guoying Xu, Yufei Ding, Yu Li, Guoqiang Yu, Tingting Qing, Yanrong Li, Juan Shen, Yiping Wang, Jian Wang, Xiumin Int J Mol Sci Article 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. MDPI 2017-04-18 /pmc/articles/PMC5412439/ /pubmed/28420223 http://dx.doi.org/10.3390/ijms18040857 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Niu
Chang, Guoying
Xu, Yufei
Ding, Yu
Li, Guoqiang
Yu, Tingting
Qing, Yanrong
Li, Juan
Shen, Yiping
Wang, Jian
Wang, Xiumin
Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency
title Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency
title_full Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency
title_fullStr Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency
title_full_unstemmed Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency
title_short Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency
title_sort clinical and molecular characterization of patients with fructose 1,6-bisphosphatase deficiency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412439/
https://www.ncbi.nlm.nih.gov/pubmed/28420223
http://dx.doi.org/10.3390/ijms18040857
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