Transcriptome analysis of cell culture from patients with Richieri-Costa-Pereira Syndrome

• Grant number: 17/01716-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2017
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Maria Rita dos Santos e Passos Bueno
• Grantee: Giovanna Pontillo Guimarães
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Richieri-Costa-Pereira syndrome (RCPS) is a rare autosomal-recessive craniofacial disease characterized by defects of jaw fusion, micrognathia, glossoptosis, and bone anomalies. RCPS is caused by expansions in the 5'UTR region of the EIF4A3 gene, which leads to a decrease on its expression levels. EIF4A3 exerts basic cellular functions related to mRNA processing. The clinical set of RCPS suggests disorders in neural crest cell (NCC) development during embryogenesis. We performed RNA sequencing in NCCs from patients and controls to evaluate if lower levels of EIF4A3 interfere in the processing or expression of other important transcripts for craniofacial development. RNA sequencing results will be used to identify if differentially expressed genes and changes in alternative splicing are related to RCPS etiology. The identified transcripts will be validated with the use of real-time quantitative PCR and conventional PCR/Sanger sequencing. Candidate transcripts will be selected based on their functional relevance to the disease. The results generated by this project will be important to clarify how basic genetic/cellular mechanisms result in craniofacial malformations, and they will also open possibilities for research on therapeutic strategies. (AU)