Molecular characterization of autosomal recessive Glycogen storage disease type Ib in a Pakistani family

Objective: To investigate Glycogen storage disease GSD type Ib in a Pakistani family through whole exome sequencing (WES) and Sanger sequencing to identify the genetic mutation and confirm its autosomal recessive inheritance. Methods: This case-control and observational study was conducted at Isla...

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Main Authors: Zeeshan Nazir, Musharraf Jelani, Naveed Wasif, Fakhar Alam
Format: Article
Language:English
Published: Khyber Medical University 2025-03-01
Series:Khyber Medical University Journal
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Online Access:https://www.kmuj.kmu.edu.pk/article/view/23808
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Summary:Objective: To investigate Glycogen storage disease GSD type Ib in a Pakistani family through whole exome sequencing (WES) and Sanger sequencing to identify the genetic mutation and confirm its autosomal recessive inheritance. Methods: This case-control and observational study was conducted at Islamia College University Peshawar, Pakistan, in the laboratory of Center for Omic Sciences in collaboration with Ulm University, Germany within a period of one year. Comprehensive clinical evaluations, comprising radiological examinations and liver function tests, established the diagnosis of GSD in the index patient, who presented with hepatomegaly, oral ulcerations, night tremors, short stature and delayed speech development as compared to her normal age controls and laboratory results indicated hypoglycemia and hyperuricemia. Whole exome sequencing (WES) was performed on the index patient to identify mutations in the SLC37A4 gene, followed by Sanger sequencing of family members to confirm the autosomal recessive inheritance of the recognized mutation. Results: It is estimated that 80% of GSD-I patients have type I-a and only 20% are affected with type I-b. The analysis revealed a previously reported alteration (c.92-94del; p.Phe31del) in the SLC37A4 gene, found in a homozygous state in the affected sibling, while obligate carriers were heterozygous. The variant was absent in fifty healthy controls from the same ethnic background. Conclusion: The study highlights the role of WES and Sanger sequencing in the diagnosis of rare diseases like GSD-Ib and recommends genetic testing of close relatives to assess carrier status and guide informed reproductive and clinical decisions in order to prevent recurrence.
ISSN:2305-2643
2305-2651