Genetic screening for IRF6 and GRHL3 in Brazilians with non-syndromic cleft lip/palate / Triagem genética de IRF6 e GRHL3 em brasileiros com fissura lábio/palato não sindrômica
DOI:
https://doi.org/10.34117/bjdv6n2-237Keywords:
cleft lip, cleft palate, missense mutation, orofacial clefts, polymorphism.Abstract
Cleft lip with or without cleft palate (CL/P) is the most frequent craniofacial anomaly. Advances in molecular and quantitative analysis suggests that the etiology is multifactorial of nonsyndromic CL/P (NSCL/P), and provide new opportunities to identify genes and gene-environment interactions relevant to the etiology of this common and representative birth defect. The present study aimed at detecting genetic variants in IRF6 and GRHL3 genes and susceptibility to NSCL/P in West Central and Northern Brazilian populations. We analyzed a set of 80 individuals with NSCL/P from Associação de Combate as Deformidades Faciais, recruited from Midwest and Northern Brazil. We performed Multiplex Ligation-dependent Probe Amplification (P304-B1-IRF6/GRHL3 (Lot B1-0116)) and PCR analysis for confirmation. In the MPLA study exon 4 of GRHL3, show possible alteration. Therefore, we performed a PCR validation of these alterations. The results showed no alteration on these genes (IRF6 and GRHL3) corroborating with previous studies. To our knowledge, this study of both genes is the first in these specific areas of Brazil, analyzing individuals with NSCL/P. Studies have identified a missense variant in the gene grainyhead-like-3 (GRHL3) in cleft palate individuals. The contribution of these genetic variants to NSCL/P susceptibility should be further investigated in different populations and cohorts. Thus, the underlying genetic causes of NSCL/P remain largely unknown.
References
- Azevedo CMS, Machado RA, Martelli-Júnior H, Reis SRA, Persuhn DC, Coletta RD, Rangel ALCA. Exploring GRHL3 polymorphisms and SNP-SNP interactions in the risk of non-syndromic oral clefts in the Brazilian population. Oral Dis. 2020;26(1):145–151. doi:10.1111/odi.13204
- Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nat Rev Genet. 2011;12(3):167–178. doi:10.1038/nrg2933
- Brito LA, Bassi CF, Masotti C, Bueno DF, Cruz LA, Barbara LK, Bertola DR, Meyer D, Franco D, Alonso N, Passos-Bueno MR. IRF6 is a risk factor for nonsyndromic cleft lip in the Brazilian population. Am J Med Genet A. 2012;158A(9):2170–2175. doi:10.1002/ajmg.a.35526
- Martelli-Júnior H, Bonan PR, Santos RC, Barbosa DR, Swerts MS, Coletta RD. An epidemiologic study of lip and palate clefts from a Brazilian reference hospital. Quintessence Int. 2008;39(9):749–752.
- Rodrigues K, Sena MF, Roncalli AG, Ferreira MA. Prevalence of orofacial clefts and social factors in Brazil. Braz Oral Res. 2009;23(1):38–42. doi:10.1590/s1806-83242009000100007
- Monlleó IL, Barros AG, Fontes MI, Andrade AK, Brito GM, Nascimento DL, Gil-da-Silva-Lopes VL. Diagnostic implications of associated defects in patients with typical orofacial clefts. J Pediatr (Rio J). 2015;91(5):485–492. doi:10.1016/j.jped.2014.12.001
- Paranaíba LM, Martelli-Júnior H, Oliveira Swerts MS, Line SR, Coletta RD. Novel mutations in the IRF6 gene in Brazilian families with Van der Woude syndrome. Int J Mol Med. 2008;22(4):507–511
- Mangold E, Ludwig KU, Nöthen MM. Breakthroughs in the genetics of orofacial clefting. Trends Mol Med. 2011;17(12):725–733. doi:10.1016/j.molmed.2011.07.007
- do Rego Borges A, Sá J, Hoshi R, Viena CS, Mariano LC, de Castro Veiga P, Medrado AP, Machado RA, de Aquino SN, Messetti AC, Spritz RA, Coletta RD, Reis SR. Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Brazilian population with high African ancestry. Am J Med Genet A. 2015;167A(10):2344–2349. doi:10.1002/ajmg.a.37181
- Leslie EJ, Liu H, Carlson JC, Shaffer JR, Feingold E, Wehby G, Laurie CA, Jain D, Laurie CC, Doheny KF, McHenry T, Resick J, Sanchez C, Jacobs J, Emanuele B, Vieira AR, Neiswanger K, Standley J, Czeizel AE, Deleyiannis F, Christensen K, Munger RG, Lie RT, Wilcox A, Romitti PA, Field LL, Padilla CD, Cutiongco-de la Paz EM, Lidral AC, Valencia-Ramirez LC, Lopez-Palacio AM, Valencia DR, Arcos-Burgos M, Castilla EE, Mereb JC, Poletta FA, Orioli IM, Carvalho FM, Hecht JT, Blanton SH, Buxó CJ, Butali A, Mossey PA, Adeyemo WL, James O, Braimah RO, Aregbesola BS, Eshete MA, Deribew M, Koruyucu M, Seymen F, Ma L, de Salamanca JE, Weinberg SM, Moreno L, Cornell RA, Murray JC, Marazita ML. A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3. Am J Hum Genet. 2016;98(4):744–754. doi:10.1016/j.ajhg.2016.02.014
- de Lima RL, Hoper SA, Ghassibe M, Cooper ME, Rorick NK, Kondo S, Katz L, Marazita ML, Compton J, Bale S, Hehr U, Dixon MJ, Daack-Hirsch S, Boute O, Bayet B, Revencu N, Verellen-Dumoulin C, Vikkula M, Richieri-Costa A, Moretti-Ferreira D, Murray JC, Schutte BC. Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome. Genet Med. 2009;11(4):241–247. doi:10.1097/GIM.0b013e318197a49a
- Bezerra JF, Silva HPVD, Bortolin RH, Luchessi AD, Ururahy MAG, Loureiro MB, Gil-da-Silva-Lopes VL, Almeida MG, Amaral VS, Rezende AA. IRF6 polymorphisms in Brazilian patients with non-syndromic cleft lip with or without palate [published online ahead of print, 2019 Jun 8]. Braz J Otorhinolaryngol. 2019;S1808-8694(18)30495-6. doi:10.1016/j.bjorl.2019.04.011
- Peyrard-Janvid M, Leslie EJ, Kousa YA, Smith TL, Dunnwald M, Magnusson M, Lentz BA, Unneberg P, Fransson I, Koillinen HK, Rautio J, Pegelow M, Karsten A, Basel-Vanagaite L, Gordon W, Andersen B, Svensson T, Murray JC, Cornell RA, Kere J, Schutte BC. Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development. Am J Hum Genet. 2014;94(1):23–32. doi:10.1016/j.ajhg.2013.11.009
- de la Garza G, Schleiffarth JR, Dunnwald M, Mankad A, Weirather JL, Bonde G, Butcher S, Mansour TA, Kousa YA, Fukazawa CF, Houston DW, Manak JR, Schutte BC, Wagner DS, Cornell RA. Interferon regulatory factor 6 promotes differentiation of the periderm by activating expression of Grainyhead-like 3 [published correction appears in J Invest Dermatol. 2013 Mar;133(3):859]. J Invest Dermatol. 2013;133(1):68–77. doi:10.1038/jid.2012.269
- Mangold E, Böhmer AC, Ishorst N, Hoebel AK, Gültepe P, Schuenke H, Klamt J, Hofmann A, Gölz L, Raff R, Tessmann P, Nowak S, Reutter H, Hemprich A, Kreusch T, Kramer FJ, Braumann B, Reich R, Schmidt G, Jäger A, Reiter R, Brosch S, Stavusis J, Ishida M, Seselgyte R, Moore GE, Nöthen MM, Borck G, Aldhorae KA, Lace B, Stanier P, Knapp M, Ludwig KU. Sequencing the GRHL3 Coding Region Reveals Rare Truncating Mutations and a Common Susceptibility Variant for Nonsyndromic Cleft Palate. Am J Hum Genet. 2016;98(4):755–762. doi:10.1016/j.ajhg.2016.02.013
- Wang Y, Sun Y, Huang Y, Pan Y, Jia Z, Ma L, Ma L, Lan F, Zhou Y, Shi J, Yang X, Zhang L, Jiang H, Jiang M, Yin A, Cheng J, Wang L, Yang Y, Shi B. Association study between Van der Woude Syndrome causative gene GRHL3 and nonsyndromic cleft lip with or without cleft palate in a Chinese cohort. Gene. 2016;588(1):69–73. doi:10.1016/j.gene.2016.04.045
- He M, Bian Z. Lack of Association between Missense Variants in GRHL3 (rs2486668 and rs545809) and Susceptibility to Non-Syndromic Orofacial Clefts in a Han Chinese Population. PLoS One. 2016 Jul 26;11(7):e0159940. doi: 10.1371/journal.pone.0159940. eCollection 2016.
- Kerameddin S, Namipashaki A, Ebrahimi S, Ansari-Pour N. IRF6 Is a Marker of Severity in Nonsyndromic Cleft Lip/Palate. J Dent Res. 2015;94(9 Suppl):226S–32S. doi:10.1177/0022034515581013
- Velázquez-Aragón JA, Alcántara-Ortigoza MA, Estandia-Ortega B, Reyna-Fabián ME, Méndez-Adame CD, González-Del Angel A. Gene Interactions Provide Evidence for Signaling Pathways Involved in Cleft Lip/Palate in Humans. J Dent Res. 2016;95(11):1257–1264. doi:10.1177/0022034516647034
- de Souza LT, Kowalski TW, Ferrari J, Monlléo IL, Ribeiro EM, de Souza J, Fett-Conte AC, de Araujo TK, Gil-da-Silva-Lopes VL, Ribeiro-Dos-Santos ÂKC, dos Santos SEB, Félix TM. Study of IRF6 and 8q24 region in non-syndromic oral clefts in the Brazilian population. Oral Dis. 2016;22(3):241–245. doi:10.1111/odi.12432
- Paranaíba LM, Bufalino A, Martelli-Júnior H, de Barros LM, Graner E, Coletta RD. Lack of association between IRF6 polymorphisms (rs2235371 and rs642961) and non-syndromic cleft lip and/or palate in a Brazilian population. Oral Dis. 2010;16(2):193–197. doi:10.1111/j.1601-0825.2009.01627.x
- Wu-Chou YH, Lo LJ, Chen KT, Chang CS, Chen YR. A combined targeted mutation analysis of IRF6 gene would be useful in the first screening of oral facial clefts. BMC Med Genet. 2013;14:37. Published 2013 Mar 20. doi:10.1186/1471-2350-14-37
- Letra A, Fakhouri W, Fonseca RF, et al. Interaction between IRF6 and TGFA genes contribute to the risk of nonsyndromic cleft lip/palate. PLoS One. 2012;7(9):e45441. doi:10.1371/journal.pone.0045441
- Eshete MA; Liu H; Li M; Adeyemo WL; Gowans LJJ; Mossey PA; Busch T; Deressa W; Donkor P; Olaitan PB; Aregbesola BS; Braimah RO; Oseni GO; Oginni F; Audu R; Onwuamah C; James O; Augustine-Akpan E; Rahman LA; Ogunlewe MO; Arthur FKN; Bello SA; Agbenorku P; Twumasi P; Abate F; Hailu T; Demissie Y; Hailu A; Plange-Rhule G; Obiri-Yeboah S; Dunnwald MM; Gravem PE; Marazita ML; Adeyemo AA; Murray JC; Cornell R; Butali A. Loss-of-Function GRHL3 Variants Detected in African Patients with Isolated Cleft Palate. J Dent Res. 2018;97(1):41–48. doi:10.1177/0022034517729819
