A novel Gly436Glu variant in the LPL gene identified in a Saudi Arabian patient with severe hypertriglyceridemia and recurrent pancreatitis

Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis, often manifesting in childhood. The condition results from variants in the lipoprotein lipase (LPL) gene, which lead to impaired fat metabolism. We...

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Main Authors: Dena A. Nuwaylati, Hussam Daghistani, Noor Ahmad Shaik, Zuhier A. Awan
Format: Article
Language:English
Published: Sungkyunkwan University School of Medi 2024-12-01
Series:Precision and Future Medicine
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Online Access:http://pfmjournal.org/upload/pdf/pfm-2024-00163.pdf
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author Dena A. Nuwaylati
Hussam Daghistani
Noor Ahmad Shaik
Zuhier A. Awan
author_facet Dena A. Nuwaylati
Hussam Daghistani
Noor Ahmad Shaik
Zuhier A. Awan
author_sort Dena A. Nuwaylati
collection DOAJ
description Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis, often manifesting in childhood. The condition results from variants in the lipoprotein lipase (LPL) gene, which lead to impaired fat metabolism. We report the case of an 18-year-old Saudi male with a lifelong history of hypertriglyceridemia and recurrent episodes of pancreatitis. Laboratory investigations revealed severe hypertriglyceridemia and low high-density lipoprotein cholesterol, consistent with FCS. A comprehensive evaluation excluded secondary causes of hyperlipidemia, suggesting a potential genetic basis for the condition. Whole-exome sequencing identified a novel homozygous missense variant (c.1307G> A; p.Gly436Glu) in the LPL gene. Bioinformatics analysis predicted this variant to be deleterious, potentially disrupting the structure and stability of the LPL enzyme and impairing its ability to hydrolyze dietary fats. This finding suggested a causal link between the variant and the patient’s FCS phenotype. This case highlights the importance of molecular diagnosis in FCS, enabling the identification of causative genetic alterations and improving our understanding of the link between LPL dysfunction and severe metabolic disorders.
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spelling doaj-art-5abb0bd8c92e4e2db4231b2f3832fcca2025-08-20T03:33:26ZengSungkyunkwan University School of MediPrecision and Future Medicine2508-79402508-79592024-12-018417818310.23838/pfm.2024.00163178A novel Gly436Glu variant in the LPL gene identified in a Saudi Arabian patient with severe hypertriglyceridemia and recurrent pancreatitisDena A. Nuwaylati0Hussam Daghistani1Noor Ahmad Shaik2Zuhier A. Awan3 Department of Clinical Biochemistry, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia Department of Clinical Biochemistry, Faculty of Medicine, University of Jeddah, Jeddah, Saudi ArabiaFamilial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis, often manifesting in childhood. The condition results from variants in the lipoprotein lipase (LPL) gene, which lead to impaired fat metabolism. We report the case of an 18-year-old Saudi male with a lifelong history of hypertriglyceridemia and recurrent episodes of pancreatitis. Laboratory investigations revealed severe hypertriglyceridemia and low high-density lipoprotein cholesterol, consistent with FCS. A comprehensive evaluation excluded secondary causes of hyperlipidemia, suggesting a potential genetic basis for the condition. Whole-exome sequencing identified a novel homozygous missense variant (c.1307G> A; p.Gly436Glu) in the LPL gene. Bioinformatics analysis predicted this variant to be deleterious, potentially disrupting the structure and stability of the LPL enzyme and impairing its ability to hydrolyze dietary fats. This finding suggested a causal link between the variant and the patient’s FCS phenotype. This case highlights the importance of molecular diagnosis in FCS, enabling the identification of causative genetic alterations and improving our understanding of the link between LPL dysfunction and severe metabolic disorders.http://pfmjournal.org/upload/pdf/pfm-2024-00163.pdfhomozygotehypertriglyceridemialipoprotein lipasepancreatitis
spellingShingle Dena A. Nuwaylati
Hussam Daghistani
Noor Ahmad Shaik
Zuhier A. Awan
A novel Gly436Glu variant in the LPL gene identified in a Saudi Arabian patient with severe hypertriglyceridemia and recurrent pancreatitis
Precision and Future Medicine
homozygote
hypertriglyceridemia
lipoprotein lipase
pancreatitis
title A novel Gly436Glu variant in the LPL gene identified in a Saudi Arabian patient with severe hypertriglyceridemia and recurrent pancreatitis
title_full A novel Gly436Glu variant in the LPL gene identified in a Saudi Arabian patient with severe hypertriglyceridemia and recurrent pancreatitis
title_fullStr A novel Gly436Glu variant in the LPL gene identified in a Saudi Arabian patient with severe hypertriglyceridemia and recurrent pancreatitis
title_full_unstemmed A novel Gly436Glu variant in the LPL gene identified in a Saudi Arabian patient with severe hypertriglyceridemia and recurrent pancreatitis
title_short A novel Gly436Glu variant in the LPL gene identified in a Saudi Arabian patient with severe hypertriglyceridemia and recurrent pancreatitis
title_sort novel gly436glu variant in the lpl gene identified in a saudi arabian patient with severe hypertriglyceridemia and recurrent pancreatitis
topic homozygote
hypertriglyceridemia
lipoprotein lipase
pancreatitis
url http://pfmjournal.org/upload/pdf/pfm-2024-00163.pdf
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