Search for molecular pathways and protein partners of CNTN6 in craniogenesis regulation

Introduction: Copy number variations of single gene (CNVs), that have been described in patients with intellectual disability, frequently affect not only the central nervous system, but also some other systems. We and other authors have shown that isolated microdeletions and microduplcations of CNTN6 gene in patients with intellectual disability were accompanied by cranial malformations, facial dysmorphism, scoliosis, cardiological abnormalities, and seizures. However, it is unclear what underlies this effect. Aim. This work aims to search for molecular pathways and partners of CNTN6 that may regulate craniogenesis. Materials and methods. The molecular karyotyping for 117 children of 3-17 years old with developmental delay, intellectual disability and dysmorphic features was performed using 44K and 60K arrays (Agilent Technologies). The analysis of possible molecular interactions of CNTN6 and proteins encoded by genes of likely pathogenic CNVs was done by STRING gene networks. Results. Pathogenic and potentially pathogenic CNVs were found in 30 patients, among which 24 patients had skull anomalies. For three children with isolated CNTN6 mutation the Notch and CAM signaling pathways with NOTCH1 and ALCAM participating in osteogenesis appeared to be significant. When building gene networks for the 17 patients with the CNVs, affecting other chromosomal regions, with skull abnormalities (N = 11) and without them (N = 6), the involvement of CAM pathway genes was shown for one more child with skull anomaly. Notch signaling pathway was found in both groups. Conclusions. Skull anomalies in patients with CNTN6 microdeletions and microduplications are more likely mediated by CAM signaling pathway through the interaction of CNTN6 with the product of ALCAM gene

краниогенез, вариации числа копий участков ДНК, CNTN6, CAM сигнальный путь, ALCAM, craniogenesis, DNA copy number variation, CNTN6, CAM signaling pathway, ALCAM

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