Background: Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. Method: In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was intellectual disability. The most frequently overrepresented GO biological process, cellular component and molecular function terms were regulation of membrane potential, ion channel complex, voltage-gated ion channel activity/voltage-gated channel activity, respectively. Conclusion: Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.

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<b><i>Introduction:</i></b> Congenital glycosylation disorders are multisystem diseases with heterogeneous clinical manifestations caused by defects in the synthesis of the glycan moiety of glycoproteins or glycolipids or the binding of glycans to proteins and lipids. DPAGT1 (UDP-GlcNAc: dolichol phosphate N-acetylglucosamine-1-phosphotransferase) is an initiating protein in the biosynthetic pathway of dolichol-linked oligosaccharides required for protein N-glycosylation. Pathogenic variants in <i>DPAGT1</i> (UDP-GlcNAc: dolichol phosphate N-acetylglucosamine-1-phosphotransferase) gene cause a rare type of congenital glycosylation disorder called DPAGT1-CDG (formerly CDG-Ij) (OMIM #608093). It is a rare autosomal recessive disease or a milder version with congenital myasthenic syndrome known as DPAGT1-CMS. A severe disease course with hypotonia, cataracts, skeletal deformities, resistant epilepsy, intellectual disability, global developmental delay, premature death has been described in most patients with DPAGT1-CDG. <b><i>Patient Presentation:</i></b> We describe two patients with variants in the <i>DPAGT1</i> gene: an 8-month-old boy with a homozygous, missense <i>DPAGT1</i>:c.339T&#x3e;G (p.Phe113Leu) novel variant and a 13-year-old female patient with compound heterozygous variants, <i>DPAGT1</i>:c.466C&#x3e;T (p.Arg156Cys, R156C) and <i>DPAGT1</i>:c.161+5G&#x3e;A. While the 8-month-old patient was diagnosed with congenital cataract at the age of 1 month, had dysmorphic findings, and epilepsy, clinical symptoms in the other patient appeared later but with more prominent muscle weakness, behavioral disorder, dysmorphic findings, and no epilepsy. <b><i>Discussion:</i></b> Cholinesterase inhibitor therapy was found to be effective in patients against muscle weakness, supporting <i>DPAGT1</i> deficiency as the underlying etiology. We started pyridostigmine treatment in our patient with more pronounced muscle weakness, and we saw its benefit. We aimed to present our patients diagnosed with DPAGT1-CDG due to different variants in the same gene and different clinical presentations, treatment and to compare them with other patients in the literature.

The hemogram parameters have been extensively discussed in numerous diseases, including epilepsy, for their diagnostic and prognostic values. We aimed to investigate the impact of hemogram parameters, namely, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) at the time of the first seizure on the remission durations of the patients with self-limited epilepsy with centrotemporal spikes (SeLECTS). This retrospective study was conducted on patients with SeLECTS with a minimum follow-up of 2 years. We assessed the hemogram parameters obtained from the venous blood samples collected from the patients upon admission. The duration of remission was categorized into two groups for further data analysis: those with a remission period less than 2 years and those with a remission period of more than 2 years. This study involved 122 patients with SeLECTS, of which 85% (n = 102) had remission durations of ≤2 years. The analysis revealed that patients with remission durations exceeding 2 years had a significantly higher median leukocyte (p = 0.009), neutrophil (p < 0.001), and platelet (p < 0.001) counts. Additionally, higher levels of NLR and PLR were observed in patients with longer-term remission (p < 0.001). However, there were no significant differences between the two groups in terms of lymphocyte count, monocyte count, mean platelet volume, or LMR. Leukocyte, neutrophil, platelet, NLR, and PLR counts have shown potential as predictive indicators of remission times in patients with SeLECTS. Neurologists can potentially find value in these easily accessible parameters when evaluating the future trajectory of patients with SeLECTS.

Early infantile epileptic encephalopathy 23 (EIEE23; OMIM #615859) is a rare autosomal recessive disorder. It is characterized by refractory seizures, multifocal epileptic activity on electroencephalography, psychomotor development delay, dysmorphic facial features and cortical blindness/visual impairment. DOCK7 is involved in intracellular signaling networks and plays a role in axon formation and neuronal polarization. Function loss of this gene has previously been described in the molecular etiology of EIEE23. Here, we report a boy with a pathogenic novel variant in the DOCK7 gene presenting with, infantile-onset epileptic encephalopathy, severe neurodevelopmental delay, dysmorphic facial features, cortical blindness as well as previously unreported minor dental and extremity anomalies. Few cases with DOCK7 mutations have been reported in the literature. Due to its high genetic heterogeneity and scarcity, it is extremely important to report a novel and specific mutations and their associated clinical phenotypes. Whole exome sequencing revealed a novel pathogenic homozygous frameshift variant which has not been reported (c.5669dup (p.Cys1891ValfsTer2) mutation in the exon 44 of DOCK7).