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Hatem Zayed

Publications and source records attributed to Hatem Zayed.

2 recordsLinked to original sources
PubMed2025

Spectrum of genetic variants associated with maple syrup urine disease in the Middle East, North Africa, and Türkiye (MENAT): a systematic review.

BACKGROUND: Maple syrup urine disease (MSUD) is a hereditary metabolic disorder caused by a deficiency in the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. The Middle East and North Africa, and Türkiye (MENAT) region has witnessed a significant rise in the prevalence of MSUD due to high rates of consanguinity. Despite numerous genetic association studies, the complex relationships between genotype and phenotype in MSUD remain elusive. AIM: This study aimed to systematically review the variants significantly associated with MSUD in the MENAT region. METHODS: We systematically searched four literature databases (PubMed, Scopus, Web of Science, and Science Direct) from inception until December 2023 to gather all reported genetic data pertaining to MSUD in the MENAT region. Quality assessment and data extraction were diligently performed by a team of six investigators. RESULTS: A total of 16 studies, involving patients, were included in this systematic review. Among them, 211 patients presented with 105 variants located within genes known to be associated with MSUD. The majority of the identified MSUD variants were found in BCKDHA (38%), followed by BCKDHB (38%), DBT (23%), and PPM1K (1%). Notably, 77% of the captured variants were unique to the MENAT region. CONCLUSION: Our systematic review reveals a distinctive genetic and clinical susceptibility profile of MSUD among individuals from the MENAT region. These findings highlight the importance of understanding the specific genetic landscape of MSUD in this population. Further research is warranted to elucidate the complex genotype-phenotype relationships in MSUD in the MENAT region.

Humans↗
PubMed2023

A new horizon in the phosphorylated sites of AGA: the structural impact of C163S mutation in aspartylglucosaminuria through molecular dynamics simulation.

Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by insufficient aspartylglucosaminidase (AGA) activity leading to chronic neurodegeneration. We utilized the PhosphoSitePlus tool to identify the AGA protein's phosphorylation sites. The phosphorylation was induced on the specific residue of the three-dimensional AGA protein, and the structural changes upon phosphorylation were studied via molecular dynamics simulation. Furthermore, the structural behaviour of C163S mutation and C163S mutation with adjacent phosphorylation was investigated. We have examined the structural impact of phosphorylated forms and C163S mutation in AGA. Molecular dynamics simulations (200 ns) exposed patterns of deviation, fluctuation, and change in compactness of Y178 phosphorylated AGA protein (Y178-p), T215 phosphorylated AGA protein (T215-p), T324 phosphorylated AGA protein (T324-p), C163S mutant AGA protein (C163S), and C163S mutation with Y178 phosphorylated AGA protein (C163S-Y178-p). Y178-p, T215-p, and C163S mutation demonstrated an increase in intramolecular hydrogen bonds, leading to greater compactness of the AGA forms. Principle component analysis (PCA) and Gibbs free energy of the phosphorylated/C163S mutation structures exhibit transition in motion/orientation than Wild type (WT). T215-p may be more dominant among these than the other studied phosphorylated forms. It might contribute to hydrolyzing L-asparagine functioning as an asparaginase, thereby regulating neurotransmitter activity. This study revealed structural insights into the phosphorylation of Y178, T215, and T324 in AGA protein. Additionally, it exposed the structural changes of the C163S mutation and C163S-Y178-p of AGA protein. This research will shed light on a better understanding of AGA's phosphorylated mechanism.Communicated by Ramaswamy H. Sarma.

Molecular Dynamics Simulation↗