Banca de QUALIFICAÇÃO: RAYANE FERREIRA DA SILVA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : RAYANE FERREIRA DA SILVA
DATE: 11/04/2022
TIME: 14:00
LOCAL: ICBS
TITLE:

IRF6 gene investigation in individuals a priori diagnosed with non-syndromic typical orofacial clefts or Van der Woude syndrome from Alagoas.

KEY WORDS:

Cleft lip, Cleft lip and palate, cleft palate; Van der Woude Syndrome; IRF6 gene.

PAGES: 48
BIG AREA: Ciências Biológicas
AREA: Genética
SUBÁREA: Genética Humana e Médica
SUMMARY:

Typical orofacial clefts (TOC) are among the most frequent human malformations, with a prevalence rate of 1:700 to 1000 live births. IRF6 gene (Interferon Regulatory Factor 6) variants have been implicated worldwide in cases of familial non-syndromic TOC and in the Van der Woude syndrome (VWS). This study aimed to investigate the IRF6 gene in individuals a priori diagnosed with TOCNS or VWS from the Ambulatório de Genética Craniofacial do Serviço de Genética Clínica do Hospital Universitário Professor Alberto Antunes. The sample comprises 255 individuals presenting NSTOC and a case of VWS clinically recognized. Sociodemographic and clinical data were excepted from the Brazilian Database on Craniofacial Anomalies. It was used Excel for tabulation and EpiInfo for analysis. Fisher test and Qui-square were used for statistics with a p-value of 0,05.  The sample comprises 255 individuals presenting NSTOC and a case of VWS clinically recognized. Sociodemographic and clinical data were excepted from the Brazilian Database on Craniofacial Anomalies. It was used Excel for data tabulation and EpiInfo for statistics. Fisher test and Qui-square were used with a p-value of 0,05.  29 familial NSTOC and VWS cases were selected for the molecular study. Experiments comprised: DNA extraction, polymerase chain reaction (PCR), and Sanger sequencing of the IRF6 gene. Identified variants were checked against free access databases. In silico predictive analyses and amino acid species conservation analysis were used with classification purpose of the new variants. Between 2009 and 2021, 375 individuals entered the Alagoas database, 256 of which presented TOC, 71.6% being non-syndromic. Male biologic sex (55,8%), unilateral (74,2%), left-sided (51,0%) cleft lip and palate (51,0%) predominance corroborated the literature. There were 97 (38,6%) familial cases, almost twice the expected frequency. No IRF6 pathogenic variants among familial NSTOC were yet identified. The new missense p.Phe266Ser heterozygous (TTT/TCT) variant was identified in the case of VWS. The new variant was scored as pathogenic in the in silico analyses, the Phe266 amino acid is highly conserved among species. Moreover, there is evidence that biochemistry differences between phenylalanine and serine result in polarity and interaction changes of the protein. Preliminary results show the sociodemographic and clinical characteristics of the sample are similar to the literature, except for the high rate of familial cases. The IRF6 gene was not involved in parent-sibling transmission. The p.Phe266Ser variant is pathogenic and has been involved in the VWS phenotype in the reported case.

BANKING MEMBERS:
Presidente - 3221982 - ISABELLA LOPES MONLLEO
Interna - 2269479 - CAROLINNE DE SALES MARQUES
Externa ao Programa - 3140606 - THALITA CRISTINA FIGUEIREDO CUNHA