Identification of two novel variants in GNPTAB underlying mucolipidosis II in a Pakistani family
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Muhammad Aman Khan
Abstract
Background
Mucolipidosis II is a rare inherited metabolic disorder characterized by multiple pathologies including coarse facial features, thickened skin, dysostosis multiplex, and skeletal abnormalities. The disorder results due to variants in GNPTAB leading to reduced activity of the enzyme GlcNAc-1-phosphotransferase (GlcNAc-PT).
Methods
In the present study, a consanguineous Pakistani family was diagnosed with MLII based on clinical and biochemical examination. Peripheral blood samples were collected and subjected to DNA sequencing of all coding exons along with exon-intron boundaries of GNPTAB.
Results
Molecular investigation of the family identified two novel variants c.25C > T: p.Gln9* (maternal allele) in exon 1 and c.1160C > T: p.Ala387Val (paternal allele) in exon 10 segregating in compound heterozygous form in the affected individuals.
Conclusions
The GNPTAB variant c.25C > T variant is highly plausible to undergo nonsense-mediated mRNA decay, while the GNPTAB variant c.1160C > T is located in a highly conserved domain, thus both the variants predict to lead to affect the enzyme activity. Two novel variants have been identified in GNPTAB as the underlying cause of ML-II in a Pakistani family. The study thus expands the available GNPTAB mutation spectrum.
Acknowledgments
The authors are grateful to all the individuals who participated in the study. Muhammad Aman Khan is supported by the Indigenous PhD Fellowship from the Higher Education Commission of Pakistan.
Author contributions: Muhammad Aman Khan: data curation, methodology, conceptualization. Bibi Zubaida: patient recruitment, methodology, conceptualization, writing – review and edit. Noreen Karim: conceptualization, methodology, writing – original draft, review, and edit. Huma Arshad Cheema: patient recruitment, conceptualization, clinical and diagnostic study. Muhammad Naeem: conceptualization, funding acquisition, methodology, supervision, writing – review and edit. All 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.
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Articles in the same Issue
- Frontmatter
- Reviews
- Occurrence and clinical management of nonalcoholic fatty liver disease in obesity patients: a literature review
- Does obesity have an effect on the ECG in children?
- Original Articles
- Factors associated with oxidative stress status in pediatric patients with type 1 diabetes mellitus
- The effect of concurrent resistance-aerobic training on serum cortisol level, anxiety, and quality of life in pediatric type 1 diabetes
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- Identification of two novel variants in GNPTAB underlying mucolipidosis II in a Pakistani family
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- Case Reports
- First Scandinavian case of successful pregnancy during nitisinone treatment for type 1 tyrosinemia
- A novel etiologic factor of highly elevated cholestanol levels: progressive familial intrahepatic cholestasis
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