Investigation of rare variants in affected tissue of an individual with oculoauriculofrontonasal syndrome

• Grant number: 25/24257-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2025
• End date: November 30, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Roseli Maria Zechi Ceide
• Grantee: Willian Miranda Alvim
• Host Institution: Hospital de Reabilitação de Anomalias Craniofaciais (HRAC). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Associated research grant: 25/13345-3 - Investigation of rare variants in affected tissue from an individual with oculoauriculofrontonasal syndrome., AP.R

Abstract

The oculoauriculofrontonasal syndrome (OAFNS) is a very rare condition with sporadic cases and an unknown cause. The main clinical findings include ocular hypertelorism, epibulbar dermoid, broad or bifid nose, mandibular hypoplasia, ear anomalies, preauricular tags, and the ectopic nasal bone, an exclusive radiological finding of OAFNS. Genetic investigations using next-generation sequencing in some cases described in the literature have been unsuccessful in elucidating the etiology of this condition. Factors such as the small sample size and limitations of the techniques and analyses may have influenced the identification of rare variants associated with the phenotype. Furthermore, other non-traditional mechanisms such as tissue mosaicism or epigenetic alterations may be involved. To contribute to the elucidation of the etiology of OAFNS, our group is conducting investigation of rare variants using exome sequencing in 19 individuals clinically diagnosed with this condition (an ongoing study funded by FAPESP). As part of the investigation into the genetic influence on a non-traditional inheritance model, more specifically tissue mosaicism, in the present study, we propose to perform exome sequencing of the affected tissue (ectopic nasal bone) from one of the 19 individuals mentioned above and compare the results with those obtained from the peripheral blood exome of the same individual. The positive hypothesis is that there is a difference between the rare genetic variants in the ectopic nasal bone and in the peripheral blood. (AU)