Investigation of genetic causes of neuropsychomotor developmental delay/intellectual disability in individuals with suspicion of recessive inheritance disorders

• Grant number: 22/05126-1
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2023
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Vera Lúcia Gil da Silva Lopes
• Grantee: Vera Lúcia Gil da Silva Lopes
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Isabella Lopes Monlleó ; Társis Antônio Paiva Vieira

Abstract

Neuropsychomotor developmental delay (NDD) and intellectual disability (ID) are often associated with complex and rare phenotypes, especially in populations in which consanguineous unions are frequent. Whole exome sequencing (WES), used in the vast majority of studies of inbreeding, has been shown to be effective in identifying novel disease genes and elucidating the genetic mechanisms of several of these rare conditions. Thus, the present study aims to investigate the genetic cause of NDD/ID in patients with suspected recessive inheritance conditions, contributing to the phenotypic characterization of extremely rare conditions, as well as to the identification of new candidate genes for these conditions. For this purpose, we will select 50 families from different Brazilian states, with affected individuals who are children of consanguineous couples and/or who present a phenotype with recurrence in the siblings and/or who present increased regions of homozygosity previously detected by chromosomal microarray analysis. WES will be performed for the probands and their affected siblings, as appropriate, and all detected variants will be classified following the American College of Medical Genetics criteria. The Sanger sequencing method will be used to validate detected variants by WES, only when necessary, and for segregation analysis within families. Finally, a genotype-phenotype correlation will be performed and the variants in candidate genes will be deposited in national and international databases. (AU)