Perfil genético-clínico de famílias com recorrência de fendas orofaciais não-sindrômicas atendidas no Serviço de Genética Clínica do HUPAA-UFAL, 2009-2021

Abstract

Non-syndromic Typical Orofacial Clefts (FOTNS) are craniofacial anomalies resulting from incomplete fusion of the upper lip and/or palate. Among the various genes associated with these anomalies is the IRF6 gene. HUPAA is one of the centers participating in the Cranio-Face Brasil Project, which collects clinical and genetic data from patients with FOT in hospitals in Brazil. This study aimed to describe the clinical-genetic profile of families selected for presenting recurrence of FOTNS. A total of 29 patients were studied, six of which involved parent-child transmission and who were treated at UNICAMP using the exome sequencing protocol. The study was carried out with exons 1, 2, 5, 6, and 8. Genomic DNA was obtained from total peripheral blood of the patients, using the phenol chloroform method. The DNA obtained was analyzed by Sanger sequencing. The sequences were edited and detected with the wild-type sequence of the IRF6 gene deposited in a database. The identified variants were searched in the databases. The results obtained corroborate the literature, in which 65.89% are male with CLP. Of the 23 patients studied, 17 had the entire IRF6 gene sequenced, and no pathogenic variant was found. Two variants have no clinical significance reported in the consulted databases. The c.-73T>C (rs861019), c.-75-4A>G (rs2235377) and c.667+27C>G (rs2235375) variants may be associated with FLP, expressed in the patient's phenotype. The sample size does not allow for generalizations. Despite this, there was a higher frequency of CLP followed by FL and FP, with most cases in male patients. To date, no pathogenic alterations associated with FOT have been identified in any of the 17 patients with the screening for variants for the IRF6 gene completed.