Differential expression of the IRF6 gene in the signs of Van der Woude Syndrome: Are distinct genetic modifiers operating?

Objective: The purpose of this study was to report a new variant in the Interferon Regulatory Factor 6 gene (IRF6) and to determine phenotype-genotype correlations in a family segregating Van der Woude syndrome.Methods: A five-generation family of 80 individuals segregating VWS was investigated usin...

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Published in:	Dentistry 3000 Vol. 9; no. 1
Main Authors:	Lisboa, Rosany De Oliveira, Martins, Cláudia Maria da Rocha, Santos, Maria Elisabete Silva, Pereira, Danilo Leôncio Aguiar, Carvalho, Flávia Martinez de, Orioli, Ieda Maria, Guerreiro, João Farias, Vieira, Alexandre Rezende, Santana-da-Silva, Luiz Carlos
Format:	Journal Article
Language:	English
Published:	University Library System, University of Pittsburgh 04-11-2021
Subjects:	irf6 gene orofacial clefts van der woude syndrome
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Summary:	Objective: The purpose of this study was to report a new variant in the Interferon Regulatory Factor 6 gene (IRF6) and to determine phenotype-genotype correlations in a family segregating Van der Woude syndrome.Methods: A five-generation family of 80 individuals segregating VWS was investigated using a tabulated pedigree but considering that three individuals registered in the pedigree died shortly after birth, the final sample size was 77 individuals. Five individuals had a complete dental clinical examination and molecular analysis performed using direct sequencing of the exon 4 and an adjacent region with 23 base pairs of the IRF6 gene.Results: Features of VWS reported in family history were present in 36.4% (28/77) of all family members; of these 57% (16/28) had pits in the lower lip, 36% (10/28) had both pits and orofacial clefts and 7 % (2/28) had only orofacial clefts. Developmental dental anomalies were observed in three individuals. The sequence analysis of exon 4 of the IRF6 gene carried out for 4 family members revealed the presence of the SNP rs7552506 (c.175-5C> G) located in five base pairs before the start of exon. The analysis of exon 4 of the IRF6 gene also revealed a new variant c.269G>C (p.Ser90Thr) which causes exchange of the Serine amino acid residue for the Threonine residue. Conclusions: The c.269G>C(p.Ser90Thr) can interfere with multimeric interactions and with protein conformation that will be slightly destabilized, because the mutant residue is bigger than the wild-type residue. The phenotypic variations in the cases studied, despite carrying the same genetic mutation, suggest that distinct genetic modifiers operate on the formation of clefts and dental development.
ISSN:	2167-8677 2167-8677
DOI:	10.5195/d3000.2021.164