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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Ogata, Tsutomu / Toppari, Jorma

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2191-0251
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Volume 30, Issue 11

Issues

Genetic analysis of fructose-1,6-bisphosphatase (FBPase) deficiency in nine consanguineous Pakistani families

Sadaqat Ijaz
  • Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan
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/ Muhammad Yasir Zahoor
  • Corresponding author
  • Molecular Biology and Forensic Laboratory, Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore 54000, Pakistan, Phone: +92-429-921-3510
  • Email
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/ Muhammad Imran
  • Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan
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/ Khushnooda Ramzan
  • Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
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/ Munir Ahmad Bhinder
  • Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore, Pakistan
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/ Hussain Shakeel / Muhammad Iqbal
  • Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
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/ Asim Aslam / Wasim Shehzad
  • Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan
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/ Huma Arshad Cheema
  • Department of Pediatric Gastroenterology and Hepatology, The Children’s Hospital and The Institute for Child Health, Lahore, Pakistan
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/ Habib Rehman
Published Online: 2017-10-09 | DOI: https://doi.org/10.1515/jpem-2017-0188

Abstract

Background:

Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inherited metabolic disorder characterized by recurrent episodes of hypoglycemia, ketosis and lactic acidosis. FBPase is encoded by FBP1 gene and catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate in the last step of gluconeogenesis. We report here FBP1 mutations in nine consanguineous Pakistani families affected with FBPase deficiency.

Methods:

Nine families having one or two individuals affected with FBPase deficiency were enrolled over a period of 3 years. All FBP1 exonic regions including splicing sites were PCR-amplified and sequenced bidirectionally. Familial cosegregation of mutations with disease was confirmed by direct sequencing and PCR-RFLP analysis.

Results:

Three different FBP1 mutations were identified. Each of two previously reported mutations (c.472C>T (p.Arg158Trp) and c.841G>A (p.Glu281Lys)) was carried by four different families. The ninth family carried a novel 4-bp deletion (c.609_612delAAAA), which is predicted to result in frameshift (p.Lys204Argfs*72) and loss of FBPase function. The novel variant was not detected in any of 120 chromosomes from normal ethnically matched individuals.

Conclusions:

FBPase deficiency is often fatal in the infancy and early childhood. Early diagnosis and prompt treatment is therefore crucial to preventing early mortality. We recommend the use of c.472C>T and c.841G>A mutations as first choice genetic markers for molecular diagnosis of FBPase deficiency in Pakistan.

Keywords: FBPase deficiency; FBP1 gene; metabolic disorder; Pakistani population

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About the article

Corresponding author: Muhammad Yasir Zahoor, PhD, Molecular Biology and Forensic Laboratory, Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore 54000, Pakistan, Phone: +92-429-921-3510


Received: 2017-05-05

Accepted: 2017-08-14

Published Online: 2017-10-09

Published in Print: 2017-10-26


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 30, Issue 11, Pages 1203–1210, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2017-0188.

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