Understanding microdeletion syndromes: the Smith-Magenis syndrome model

Abstract

1 - Mini-course of Graduate Studies, 3 credits (45 hours/class) - Understanding Microdeletion Syndromes: The Smith-Magenis Syndrome Model. 2- Project Discussion: "Genomic analysis of the critical region of Smith-Magenis syndrome (17p11.2) for investigation of SNP variability and its correlation with phenotypic spectrum variability".Smith-Magenis syndrome (MCS) is characterized by variable-grade cognitive deficits, changes in sleep pattern, skeletal and craniofacial anomalies, self-mutilation, and delayed motor and speech development, with an occurrence of 1 every 15,000 a 25,000 live births. It is a disorder of genetic origin, caused by the deletion in the chromosomal region 17p11.2, which comprises the acid-induced retinoic gene 1 (RAI1) among other genes. The RAI1 gene seems to be the main gene involved in the syndrome, however, recent reports in the literature suggest that other genes in 17p11.2, or the presence of mutations or nucleotide variations such as SNPs (single nucleotide polymorphisms) in this segment could contribute to the phenotypic variation in cases of loss of heterozygosity. In order to increase the knowledge of the genomic alterations involved in this region, characterizing or defining the genomic profile of the syndrome, we propose the confirmation of the clinical and laboratory diagnosis (G and FISH banding) of 20 patients with STS registered with the Genetic Counseling Service -IBB / Unesp), the definition of breaking points of the region deleted by Comparative Genomic Hybridization (a-CGH) microarray analysis, and the analysis of single nucleotide polymorphisms (SNPs) in the critical region for Smith-Magenis (17p11. 2) using a sequencing panel. In addition, as a sub-project, we will use the structure assembled with the budget of this project to evaluate 20 other patients with peculiar chromosomal aberrations but with inconclusive diagnoses, and thus, with the new methodologies of analysis, we can characterize with greater precision the chromosomal anomaly and their role in the phenotype, as well as improve the accuracy of Genetic Counseling.3- meeting between Dr. Smith and members of the Brazilian Association of Smith-Maguenis Syndrome to update the management of these patients, as well as exchange of experiences, since Dr. Smith has participated in several meetings of parents in the USA - Parents and Researchers Insteresting in Smith-Magenis Syndrome (PRISMS) as in other countries such as Germany, Holland, France, etc. (AU)