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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MDPI AG
2017-04-01
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Series: | International Journal of Molecular Sciences |
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Online Access: | http://www.mdpi.com/1422-0067/18/4/857 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Niu Li Guoying Chang Yufei Xu Yu Ding Guoqiang Li Tingting Yu Yanrong Qing Juan Li Yiping Shen Jian Wang Xiumin Wang |
spellingShingle |
Niu Li Guoying Chang Yufei Xu Yu Ding Guoqiang Li Tingting Yu Yanrong Qing Juan Li Yiping Shen Jian Wang Xiumin Wang Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency International Journal of Molecular Sciences fructose-1,6-bisphosphatase (FBPase) deficiency targeted-next generation sequencing FBP1 gene functional study |
author_facet |
Niu Li Guoying Chang Yufei Xu Yu Ding Guoqiang Li Tingting Yu Yanrong Qing Juan Li Yiping Shen Jian Wang Xiumin Wang |
author_sort |
Niu Li |
title |
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_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_sort |
clinical and molecular characterization of patients with fructose 1,6-bisphosphatase deficiency |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2017-04-01 |
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. |
topic |
fructose-1,6-bisphosphatase (FBPase) deficiency targeted-next generation sequencing FBP1 gene functional study |
url |
http://www.mdpi.com/1422-0067/18/4/857 |
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doaj-d9d1fa2c0ad147cfb7db52810cfc2b2c2020-11-25T00:08:02ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-04-0118485710.3390/ijms18040857ijms18040857Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase DeficiencyNiu Li0Guoying Chang1Yufei Xu2Yu Ding3Guoqiang Li4Tingting Yu5Yanrong Qing6Juan Li7Yiping Shen8Jian Wang9Xiumin Wang10Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, ChinaDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, ChinaDepartment of Endocrinology and Metabolism, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, ChinaFructose-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.http://www.mdpi.com/1422-0067/18/4/857fructose-1,6-bisphosphatase (FBPase) deficiencytargeted-next generation sequencingFBP1 genefunctional study |