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 us...

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Autores principales:	Rosany de Oliveira Lisboa, Cláudia Maria da Rocha Martins, Maria Elisabete Silva Santos, Danilo Leôncio Aguiar Pereira, Flávia Martinez de Carvalho, Ieda Maria Orioli, João Farias Guerreiro, Alexandre Rezende Vieira, Luiz Carlos Santana-da-Silva
Formato:	article
Lenguaje:	EN
Publicado:	University Library System, University of Pittsburgh 2021
Materias:	van der woude syndrome orofacial clefts irf6 gene Dentistry RK1-715
Acceso en línea:	https://doaj.org/article/27a280c9814944cb9b98d1fb9d10a1c8
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spelling	oai:doaj.org-article:27a280c9814944cb9b98d1fb9d10a1c82021-11-04T16:12:38ZDifferential expression of the IRF6 gene in the signs of Van der Woude Syndrome: Are distinct genetic modifiers operating?2167-867710.5195/d3000.2021.164https://doaj.org/article/27a280c9814944cb9b98d1fb9d10a1c82021-11-01T00:00:00Zhttp://dentistry3000.pitt.edu/ojs/index.php/dentistry3000/article/view/164https://doaj.org/toc/2167-8677Objective: 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.Rosany de Oliveira LisboaCláudia Maria da Rocha MartinsMaria Elisabete Silva SantosDanilo Leôncio Aguiar PereiraFlávia Martinez de CarvalhoIeda Maria OrioliJoão Farias GuerreiroAlexandre Rezende VieiraLuiz Carlos Santana-da-SilvaUniversity Library System, University of Pittsburgharticlevan der woude syndromeorofacial cleftsirf6 geneDentistryRK1-715ENDentistry 3000, Vol 9, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	van der woude syndrome orofacial clefts irf6 gene Dentistry RK1-715
spellingShingle	van der woude syndrome orofacial clefts irf6 gene Dentistry RK1-715 Rosany de Oliveira Lisboa Cláudia Maria da Rocha Martins Maria Elisabete Silva Santos Danilo Leôncio Aguiar Pereira Flávia Martinez de Carvalho Ieda Maria Orioli João Farias Guerreiro Alexandre Rezende Vieira Luiz Carlos Santana-da-Silva Differential expression of the IRF6 gene in the signs of Van der Woude Syndrome: Are distinct genetic modifiers operating?
description	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.
format	article
author	Rosany de Oliveira Lisboa Cláudia Maria da Rocha Martins Maria Elisabete Silva Santos Danilo Leôncio Aguiar Pereira Flávia Martinez de Carvalho Ieda Maria Orioli João Farias Guerreiro Alexandre Rezende Vieira Luiz Carlos Santana-da-Silva
author_facet	Rosany de Oliveira Lisboa Cláudia Maria da Rocha Martins Maria Elisabete Silva Santos Danilo Leôncio Aguiar Pereira Flávia Martinez de Carvalho Ieda Maria Orioli João Farias Guerreiro Alexandre Rezende Vieira Luiz Carlos Santana-da-Silva
author_sort	Rosany de Oliveira Lisboa
title	Differential expression of the IRF6 gene in the signs of Van der Woude Syndrome: Are distinct genetic modifiers operating?
title_short	Differential expression of the IRF6 gene in the signs of Van der Woude Syndrome: Are distinct genetic modifiers operating?
title_full	Differential expression of the IRF6 gene in the signs of Van der Woude Syndrome: Are distinct genetic modifiers operating?
title_fullStr	Differential expression of the IRF6 gene in the signs of Van der Woude Syndrome: Are distinct genetic modifiers operating?
title_full_unstemmed	Differential expression of the IRF6 gene in the signs of Van der Woude Syndrome: Are distinct genetic modifiers operating?
title_sort	differential expression of the irf6 gene in the signs of van der woude syndrome: are distinct genetic modifiers operating?
publisher	University Library System, University of Pittsburgh
publishDate	2021
url	https://doaj.org/article/27a280c9814944cb9b98d1fb9d10a1c8
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Differential expression of the IRF6 gene in the signs of Van der Woude Syndrome: Are distinct genetic modifiers operating?

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