Accepted_test

Cohesin is an important protein of the mitotic cycle, involving in the cohesion of sister chromatids, in a the repair of double-stranded DNA breaks through the mechanism of homologous recombination and in interactions between cis-regulatory elements of the genome. Mutations in the cohesin complex proteins are associated with the called cohesinopathies. The best characterized of these is Cornelia de Lange syndrome, caused by mutations in the NIPBL, SMC1A or SMC3 genes . Microduplications of Xq25, including the entire STAG2 gene sequence, also cause cohesinopathies, the main phenotypic manifestations of which are: hypotonia, delayed speech development, mild to moderate mental retardation and abnormal behavior. However, the mechanism of the pathology development is unknown. Previously, two patients were identified with amplification of the Xq25 region of 377 kb (chrX:123056490-123433630, GRCh37), which affects a single gene, STAG2. The patients are half-brothers and both have developmental delays and autistic traits. The purpose of the study is to determine the role of STAG2 gene copy number variations in the early stages of brain cell development. We expect that these experiments will shed light on the molecular mechanisms of diseases resulting from Xq25 amplification.

We obtained iPS cells lines from patients with STAG2 gene duplication; we have shown that this chromosomal rearrangement leads to an increase in the expression of the STAG2 gene. We differentiated iPS cells into neural progenitor cells and analyzed their transcriptome.