Copy number variants on chromosome X  and impact in neurodevelopment disorders

• Autor(a) principal: Tiago Manuel Martins
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://hdl.handle.net/10216/150364
• topic: Medicina clínica; Clinical medicine

Introduction: Copy number variants (CNVs) on X chromosome are associated with several human diseases, especially impairment of the neurodevelopment. Several disease susceptibility regions have been identified on X chromosome, some already associated with known genetic syndromes, nonetheless others remain to be clarified. Array comparative genomic hybridization (aCGH) is a useful method to access pathogenic or likely-pathogenic CNVs in a clinical population. The main goal of this study was to provide a genotype-phenotype correlation focused on CNVs present on the X chromosome. Methods: A cross-sectional study was performed using the aCGH database of the Genetic Department of the Faculty of Medicine and clinical records from hospitals database. Patients with pathogenic or likely pathogenic CNVs on chromosome X were included in the study. Databases and related literature were used for a better understanding of the genotypephenotype correlation. Results: From 2852 patients studied using aCGH, 42 presented clinically relevant CNVs on X chromosome: 47,62% were classified as likely pathogenic and 52,38% as pathogenic. Among the 20 likely pathogenic CNVs, 5% were identified in the prenatal context, while 95% were postnatal. Concerning to the 22 pathogenic CNVs, 41% were prenatal cases and 59% were postnatal cases. Chromosomal regions Xp22.31, Xp22.32 and Xq28 exhibited a higher incidence of CNVs. Frequently Xp11.22, Xp11.3 and Xq11.2 regions showed clinically relevant CNVs. Conclusions: We contributed for a better understanding of the disease-associated CNVs on the X chromosome, especially those related with neurodevelopment disorders, allowing a more accurate diagnosis, improving genetic counseling namely in prenatal diagnosis setting.