Search for genetic variants with pathogenic potential in patients with a characteristic phenotype of coesinopathies focusing on the Cornelia de Lange Syndrome

Abstract

Coesinopathies is the name given to diseases caused by mutations in genes that are part of the protein complex called cohesin or its regulators. This complex has several functions in cellular activity and maintenance of genomic architecture. Because they are syndromes caused by mutations that affect the same structure, the phenotypes of coesinopathies often overlap, making clinical diagnosis difficult without molecular investigation. Other factors such as mosaic variants in the NIPBL gene, which are not identified in DNA obtained from peripheral blood, and variants in non-coding regions of the genome also contribute to the difficulty of clinical and molecular diagnosis of coesinopathies. Therefore, this work aims to search for new variants related to coesinopathies, especially Cornelia de Lange Syndrome, through exome sequencing using oral mucosa samples, as well as Copy Number Variations (CNVs), from SNP- array, and variants at non-coding locations in the genome, by genome sequencing. The results obtained may suggest new regions and variants of interest for the study and diagnosis of cohesinopathies, especially Cornelia de Lange Syndrome, thus increasing the knowledge of genetic factors related to the pathogenesis of cohesinopathies. (AU)