| Abstract [eng] |
Intellectual disability (ID) is a broad diagnosis encompassing a wide variety of overlapping phenotypes and severities. The leading known cause of ID currently is chromosomal alterations. The prevalence, poor curability and the lifelong severity emphasize the impact of ID and need for research. The aim of this study was to determine the phenotypic impact of pathogenic copy number variants (CNVs) and their role in disturbance of development and function of the CNS in patients with ID. 211 patients were enrolled in the study and molecular karyotyping was performed. 36 pathogenic CNVs in 29 of 211 patients were identified (diagnostic yield 13.7 %). When the cases of known microdeletion/ microduplication syndroms were excluded, the diagnostic yield in revealing cases with novel pathogenic CNVs by molecular karyotyping was 9.5 %. The comparison of the clinical data of patients with chromosomal alterations and those with normal molecular karyotyping results revealed, that congenital malformations of corpus callosum, minor anomalies of ear and brachydactyly were prognostic for chromosomal alterations phenotypic features. Analyzing unique pathogenic CNVs, phenotypic features, specific to 7p22.1 microduplication and 17q21.22 microdeletion were determined, as well as candidate genes for ID (ERBB4 CAD10 ir CACNA1G genes) and the disturbance of craniofacial development (ACTB gene) were identified. The detection of 5q35.3 microduplication was important for the identification of the region, located 63 kb upstream of the NSD1 gene, which is possibly significant for the expression of the NSD1 gene. Also complex chromosomal rearrangements were analyzed and genetic diagnostic workflow for patients with ID was established. |
