Pathogenic variants and expression of candidate genes to oculo-auriculo-vertebral spectrum (OAVS)

• Grant number: 16/18781-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2017
• End date: December 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Maria Isabel de Souza Aranha Melaragno
• Grantee: Malú Zamariolli de Souza
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 14/11572-8 - Chromosomal rearrangements and their relevance in the etiology of genetic disorders: cytogenomic and molecular investigation, AP.TEM

Abstract

The Oculo-Auriculo-Vertebral Spectrum (OAVS) comprises a set of phenotypically heterogeneous diseases that mainly involve derivatives of the first and second pharyngeal arches. Thus the most relevant phenotypes are craniofacial anomalies such as hemifacial microsomia, microtia, preauricular tags, microphthalmia as well as vertebral changes. The etiology of this spectrum is not well understood, but seems to be quite complex, involving genetic and environmental factors, such as maternal diabetes, drug and vasoactive use during pregnancy. The association of genetic factors to the disease has been made by linkage studies that showed patterns of recessive and autosomal dominant inheritance, and also by the investigation of chromosomal abnormalities found in patients diagnosed with OAVS. Moreover, some genes have been identified in the literature as candidates for the etiopathogenesis of changes in craniofacial development. Thus, this project proposes to investigate patients diagnosed with OAVS for the presence of pathogenic variants and expression changes in candidate genes to this disease. To identify structural changes in the coding regions of the selected genes, we will use the techniques of new generation sequencing followed by validation by Sanger sequencing combined with in silico analysis using bioinformatic tools. To evaluate the expression of selected genes, real time PCR will be used so that the results obtained for patients are compared with control subjects not affected by the disease. The results of these studies will allow a better understanding of the etiology of OAVS and a future detailed refinement of the genetic features that interrupt the programming of signaling pathways during development of craniofacial structures derived from the 1st and 2nd pharyngeal arches, causing the phenotypic features of patients with OAVs. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZAMARIOLLI, M.; SANTOS, L. C.; COLOVATI, M. E. S.; PEREZ, A. B.; BRAGAGNOLO, S.; MELARAGNO, M. I.. Ten candidate genes sequenced in patients with oculo-auriculo-vertebral spectrum. European Journal of Human Genetics, v. 27, p. 1-pg., 2019-07-01. (16/18781-7)