bims-meglyc 2026-03-22 papers

Issue of 2026–03–22
three papers selected by
Silvia Radenkovic, UMC Utrecht

Case Rep Neurol. 2026 Jan-Dec;18(1):18(1): 139-145

A Novel Phenotypic Presentation of Absence Seizures in a 15-Month-Old with PIGK-Related GPI Biosynthesis Disorder: A Case Report.

Shan Lateef, Amy Feldman Lewanda, Julia Weston, Sarah Bade, Jacklyn Lessard.

Introduction: PIGK-related glycosylphosphatidylinositol (GPI) biosynthesis disorder is an extremely rare neurodevelopmental condition, with only 12 cases described to date. It is caused by biallelic mutations in the PIGK gene, which encodes a catalytic subunit of the GPI transamidase complex. This enzyme facilitates the attachment of GPI anchors to proteins crucial for cellular signaling and development. Eight of the 12 described cases were reported to have seizures, but the electroclinical characteristics are not well defined.
Case Presentation: We report a 15-month-old female who presented with global developmental delay, hypotonia, oral dysphagia, nystagmus, and cerebellar atrophy on MRI. Abnormal movements occurred at 10 months of age with intermittent, brief right arm tremors initially presumed to be benign myoclonus of infancy. However, subsequent 24-h video EEG revealed classic 3-Hz generalized spike-and-wave discharges with clinical correlates of behavioral arrest previously unrecognized, confirming a diagnosis of absence seizures - a feature not previously reported in the literature for PIGK-related disorders. Whole exome sequencing confirmed biallelic PIGK pathogenic variants. To our knowledge, this is the first reported case of typical absence seizures with 3-Hz generalized spike-and-wave discharges in a very young patient with confirmed PIGK mutation. Our report expands the known electroclinical phenotype of GPI-anchor deficiencies, suggesting the need to screen for subtle generalized epilepsy syndromes like absence, among affected infants.
Conclusion: This case highlights a novel EEG phenotype in PIGK-related GPI biosynthesis disorder underscoring the relevance of early EEG evaluation in infants with this extremely uncommon neurogenetic disorder.

Keywords: Absence seizures; Electroclinical phenotype; Glycosylphosphatidylinositol biosynthesis disorder; PIGK mutation

DOI: https://doi.org/10.1159/000550598

Exp Ther Med. 2026 May;31(5): 118

Organelle homeostasis disruption: A driving force in the progression of cardiomyopathy (Review).

Yuxing Hou, Chao Li, Youyou Chen, Danfeng Zhong, Miaomiao Chai, Lijiao Mo, Senna Lin, Fangfang Huang, Qi Chen.

Cardiomyopathy is a complex heart disease with structural and functional defects of the myocardium, often leading to poor clinical outcomes. While traditional research has focused on myofibrillar pathology and ion channel dysfunction, emerging evidence indicates that organelle homeostasis serves a central role in the pathogenesis of the disease. Mitochondrial dysfunction disrupts energy metabolism, calcium handling, dynamics and mitophagy. Golgi fragmentation, impaired glycosylation and abnormal vesicular trafficking jeopardize protein maturation and secretion. Endoplasmic reticulum stress causes myocardial injury via unfolded protein response, calcium dyshomeostasis and disruptions of lipid metabolism. Lysosomal degradation is disrupted by autophagic dysfunction, enzyme dysregulation and calcium signaling abnormalities. Ribosomes regulate proteostasis by defective biogenesis, quality control and translational dysregulation. Nuclear envelope instability and intercalated disc dysfunction disrupt normal mechanical and gene regulation in the development of cardiomyopathy. In combination, these findings support the concept of cardiomyopathy as a multi-organelle network disease driven by coordinated dysfunction of interconnected organelles. This review systematically summarizes current evidence on organelle-specific and inter-organelle mechanisms underlying cardiomyopathy, highlighting how disrupted organelle homeostasis collectively contributes to disease initiation and progression.

Keywords: Golgi apparatus; cardiomyopathy; endoplasmic reticulum; intercalated disc; lysosome; mitochondria; organelle homeostasis; ribosome

DOI: https://doi.org/10.3892/etm.2026.13113

Anal Chem. 2026 Mar 17.

Dose-Dependent Inhibition of Protein Glycosylation Reveals Crosstalk between Glycosylation and Phosphorylation in EGF Signaling Pathways.

Hongyi Liu, Ding Chiao Lin, Yingwei Hu, Zhenyu Sun, Yuanyu Huang, Yuanwei Xu, Hui Zhang.

Protein glycosylation and phosphorylation play critical roles in regulating diverse cellular processes, yet their interplay remains underexplored. This study employed dose-dependent glycosylation inhibition to investigate the function of glycosylation, especially in phosphorylation in epidermal growth factor (EGF) signaling. Using quantitative proteomics, we analyzed global protein expression, glycopeptides, and phosphopeptides in EGF-stimulated and unstimulated conditions. Results revealed that glycosylation inhibition disrupted phosphorylation patterns in EGF-regulated pathways. Notably, 215 EGF-regulated phosphopeptides exhibited dose-dependent changes, with pathways such as ERBB, MAPK, and mTOR signaling being significantly affected. Protein-protein interaction analysis highlighted glycosylation-dependent modulation of phosphorylation in cytoskeletal remodeling and growth factor signaling. Correlation analysis identified site-specific glycopeptides, such as Asn568 of EGFR, that influenced phosphorylation of downstream signaling proteins. Additionally, individual proteins like RCN1 and SLC4A7 demonstrated glycosylation- and phosphorylation-regulated patterns. These findings underscored the role of glycosylation in maintaining phosphorylation-dependent signaling fidelity, providing insights into the function of glycosylation on cell signaling pathways.

DOI: https://doi.org/10.1021/acs.analchem.5c08113