چکیده: (59 مشاهده)
Glycosylphosphatidylinositol (GPI) anchors are complex glycolipid structures that tether a wide array of proteins to the cell surface, playing essential roles in neurodevelopment, synaptic function, and immune regulation. Pathogenic variants in genes involved in GPI anchor biosynthesis, attachment, and post-translational remodeling result in a heterogeneous group of inherited neurodevelopmental disorders collectively known as GPI anchor deficiencies. These conditions are clinically diverse, often presenting with developmental delay, intellectual disability, epilepsy, hypotonia, and distinctive dysmorphic features, with hyperphosphatasia serving as a hallmark in select subtypes such as hyperphosphatasia with mental retardation syndrome (HPMRS). Despite advances in next-generation sequencing and functional assays, diagnosis remains challenging due to phenotypic overlap, incomplete genotype–phenotype correlations, and variable biochemical presentation. Management is primarily supportive, emphasizing seizure control, neurodevelopmental interventions, and multidisciplinary care, as no curative therapies currently exist. This review provides a comprehensive synthesis of the current understanding of GPI anchor–related disorders, encompassing the molecular mechanisms of GPI biosynthesis, the spectrum of implicated genes, and associated clinical phenotypes. We also discuss diagnostic strategies, including biochemical and molecular approaches, and summarize current management practices while highlighting unmet therapeutic needs. By integrating molecular, clinical, and therapeutic perspectives, this review aims to enhance awareness among clinicians, geneticists, and researchers, and to provide a framework for future studies aimed at improving diagnosis, understanding disease mechanisms, and developing targeted interventions for this rare but clinically significant group of disorders.
نوع مطالعه: Review Article |
دریافت: 1404/11/10 | پذیرش: 1405/2/21
دریافت: 1404/11/10 | پذیرش: 1405/2/21
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