Role of ARHGAP29 nucleotide variants in the etiology of non-syndromic cleft lip with or without cleft palate.

Authors

  • Justyna Dąbrowska Poznan University of Medical Sciences
  • Barbara Biedziak Clinic of Craniofacial Anomalies, Poznan University of Medical Sciences, Poznan, Poland
  • Agnieszka Lasota Department of Jaw Orthopaedics, Medical University of Lublin, Lublin, Poland
  • Paweł P. Jagodziński Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland
  • Adrianna Mostowska Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Poznan, Poland

DOI:

https://doi.org/10.20883/medical.e414

Keywords:

nsCL/P, ARHGAP2, SNVs

Abstract

Aim. Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common birth defect of complex and heterogeneous aetiology. Genome-wide association studies (GWAS) of nsCL/P have identified an association for the 1p22.1 chromosomal region, in which ARHGAP29 was suggested as a candidate gene. Thus, the current study aimed to determine the contribution of the common and rare ARHGAP29 nucleotide variants to the risk of nsCL/P in the Polish population.

Material and Methods. In total,197 common nucleotide variants (SNVs) and 22 missense variants located within the ARHGAP29 locus at chromosome 1p22.1 were genotyped by SNV microarray. The study was conducted in 269 individuals with nsCL/P and 569 healthy individuals.

Results. Statistical analysis revealed that 31 common nucleotide variants located at the ARHGAP29 locus were significantly associated with the increased risk of nsCL/P. The strongest individual SNV was rs2391467 with a p-value = 2.49E-06 (OR = 1.64, 95%CI: 1.34–2.02). Besides, one potentially deleterious missense variant (rs140877322, p. Arg348Leu) was identified in a single patient with nsCLP.

Conclusion. These findings confirm ARHGAP29 as a strong candidate gene for nsCL/P, with both common and rare nucleotide variants of this gene involved in the aetiology of nsCL/P in the Polish population.

Downloads

Download data is not yet available.

References

Mossey PA, Little J, Munger RG, Dixon MJ, Shaw WC. Cleft lip and palate. The Lancet. 2009 Nov;374(9703):1773-1785. https://doi.org/10.1016/s0140-6736(09)60695-4

Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nature Reviews Genetics. 2011 Feb 18;12(3):167-178. https://doi.org/10.1038/nrg2933

Leslie EJ, Marazita ML. Genetics of cleft lip and cleft palate. American Journal of Medical Genetics Part C: Seminars in Medical Genetics. 2013 Oct 4;163(4):246-258. https://doi.org/10.1002/ajmg.c.31381

Mangold E, Ludwig KU, Nöthen MM. Breakthroughs in the genetics of orofacial clefting. Trends in Molecular Medicine. 2011 Dec;17(12):725-733. https://doi.org/10.1016/j.molmed.2011.07.007

Murray J. Gene/environment causes of cleft lip and/or palate. Clinical Genetics. 2002 May 27;61(4):248-256. https://doi.org/10.1034/j.1399-0004.2002.610402.x

Beaty TH, Marazita ML, Leslie EJ. Genetic factors influencing risk to orofacial clefts: today’s challenges and tomorrow’s opportunities. F1000Research. 2016 Nov 30;5:2800. https://doi.org/10.12688/f1000research.9503.1

Leslie EJ, Carlson JC, Shaffer JR, Butali A, Buxó CJ, Castilla EE, Christensen K, Deleyiannis FWB, Leigh Field L, Hecht JT, Moreno L, Orioli IM, Padilla C, Vieira AR, Wehby GL, Feingold E, Weinberg SM, Murray JC, Beaty TH, Marazita ML. Genome-wide meta-analyses of nonsyndromic orofacial clefts identify novel associations between FOXE1 and all orofacial clefts, and TP63 and cleft lip with or without cleft palate. Human Genetics. 2017 Jan 4;136(3):275-286. https://doi.org/10.1007/s00439-016-1754-7

Ludwig KU, Böhmer AC, Bowes J, Nikolić M, Ishorst N, Wyatt N, Hammond NL, Gölz L, Thieme F, Barth S, Schuenke H, Klamt J, Spielmann M, Aldhorae K, Rojas-Martinez A, Nöthen MM, Rada-Iglesias A, Dixon MJ, Knapp M, Mangold E. Imputation of Orofacial Clefting Data Identifies Novel Risk Loci and Sheds Light on the Genetic Background of Cleft Lip ± Cleft Palate and Cleft Palate Only.. Human Molecular Genetics. 2017 Jan 13;:ddx012. https://doi.org/10.1093/hmg/ddx012

Mostowska A, Gaczkowska A, Żukowski K, Ludwig K, Hozyasz K, Wójcicki P, Mangold E, Böhmer A, Heilmann-Heimbach S, Knapp M, Zadurska M, Biedziak B, Budner M, Lasota A, Daktera-Micker A, Jagodziński P. Common variants in DLG1 locus are associated with non-syndromic cleft lip with or without cleft palate. Clinical Genetics. 2018 Feb 11;93(4):784-793. https://doi.org/10.1111/cge.13141

Yu Y, Zuo X, He M, Gao J, Fu Y, Qin C, Meng L, Wang W, Song Y, Cheng Y, Zhou F, Chen G, Zheng X, Wang X, Liang B, Zhu Z, Fu X, Sheng Y, Hao J, Liu Z, Yan H, Mangold E, Ruczinski I, Liu J, Marazita ML, Ludwig KU, Beaty TH, Zhang X, Sun L, Bian Z. Genome-wide analyses of non-syndromic cleft lip with palate identify 14 novel loci and genetic heterogeneity. Nature Communications. 2017 Feb 24;8(1). https://doi.org/10.1038/ncomms14364

Beaty TH, Murray JC, Marazita ML, Munger RG, Ruczinski I, Hetmanski JB, Liang KY, Wu T, Murray T, Fallin MD, Redett RA, Raymond G, Schwender H, Jin S, Cooper ME, Dunnwald M, Mansilla MA, Leslie E, Bullard S, Lidral AC, Moreno LM, Menezes R, Vieira AR, Petrin A, Wilcox AJ, Lie RT, Jabs EW, Wu-Chou YH, Chen PK, Wang H, Ye X, Huang S, Yeow V, Chong SS, Jee SH, Shi B, Christensen K, Melbye M, Doheny KF, Pugh EW, Ling H, Castilla EE, Czeizel AE, Ma L, Field LL, Brody L, Pangilinan F, Mills JL, Molloy AM, Kirke PN, Scott JM, Arcos-Burgos M, Scott AF. A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nature Genetics. 2010 May 2;42(6):525-529. https://doi.org/10.1038/ng.580

Birnbaum S, Ludwig KU, Reutter H, Herms S, Steffens M, Rubini M, Baluardo C, Ferrian M, Almeida de Assis N, Alblas MA, Barth S, Freudenberg J, Lauster C, Schmidt G, Scheer M, Braumann B, Bergé SJ, Reich RH, Schiefke F, Hemprich A, Pötzsch S, Steegers-Theunissen RP, Pötzsch B, Moebus S, Horsthemke B, Kramer F, Wienker TF, Mossey PA, Propping P, Cichon S, Hoffmann P, Knapp M, Nöthen MM, Mangold E. Key susceptibility locus for nonsyndromic cleft lip with or without cleft palate on chromosome 8q24. Nature Genetics. 2009 Mar 8;41(4):473-477. https://doi.org/10.1038/ng.333

Grant SF, Wang K, Zhang H, Glaberson W, Annaiah K, Kim CE, Bradfield JP, Glessner JT, Thomas KA, Garris M, Frackelton EC, Otieno FG, Chiavacci RM, Nah H, Kirschner RE, Hakonarson H. A Genome-Wide Association Study Identifies a Locus for Nonsyndromic Cleft Lip with or without Cleft Palate on 8q24. The Journal of Pediatrics. 2009 Dec;155(6):909-913. https://doi.org/10.1016/j.jpeds.2009.06.020

Mangold E, Ludwig KU, Birnbaum S, Baluardo C, Ferrian M, Herms S, Reutter H, de Assis NA, Chawa TA, Mattheisen M, Steffens M, Barth S, Kluck N, Paul A, Becker J, Lauster C, Schmidt G, Braumann B, Scheer M, Reich RH, Hemprich A, Pötzsch S, Blaumeiser B, Moebus S, Krawczak M, Schreiber S, Meitinger T, Wichmann H, Steegers-Theunissen RP, Kramer F, Cichon S, Propping P, Wienker TF, Knapp M, Rubini M, Mossey PA, Hoffmann P, Nöthen MM. Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate. Nature Genetics. 2009 Dec 20;42(1):24-26. https://doi.org/10.1038/ng.506

Beaty TH, Murray JC, Marazita ML, Munger RG, Ruczinski I, Hetmanski JB, Liang KY, Wu T, Murray T, Fallin MD, Redett RA, Raymond G, Schwender H, Jin S, Cooper ME, Dunnwald M, Mansilla MA, Leslie E, Bullard S, Lidral AC, Moreno LM, Menezes R, Vieira AR, Petrin A, Wilcox AJ, Lie RT, Jabs EW, Wu-Chou YH, Chen PK, Wang H, Ye X, Huang S, Yeow V, Chong SS, Jee SH, Shi B, Christensen K, Melbye M, Doheny KF, Pugh EW, Ling H, Castilla EE, Czeizel AE, Ma L, Field LL, Brody L, Pangilinan F, Mills JL, Molloy AM, Kirke PN, Scott JM, Arcos-Burgos M, Scott AF. A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4. Nature Genetics. 2010 May 2;42(6):525-529. https://doi.org/10.1038/ng.580

Burke TR, Tsang SH. Allelic and phenotypic heterogeneity inABCA4mutations. Ophthalmic Genetics. 2011 Apr 21;32(3):165-174. https://doi.org/10.3109/13816810.2011.565397

Leslie EJ, Mansilla MA, Biggs LC, Schuette K, Bullard S, Cooper M, Dunnwald M, Lidral AC, Marazita ML, Beaty TH, Murray JC. Expression and mutation analyses implicate ARHGAP29 as the etiologic gene for the cleft lip with or without cleft palate locus identified by genome-wide association on chromosome 1p22. Birth Defects Research Part A: Clinical and Molecular Teratology. 2012 Sep 24;94(11):934-942. https://doi.org/10.1002/bdra.23076

Biggs LC, Naridze RL, DeMali KA, Lusche DF, Kuhl S, Soll DR, Schutte BC, Dunnwald M. Interferon regulatory factor 6 regulates keratinocyte migration. Journal of Cell Science. 2014 Apr 28;127(13):2840-2848. https://doi.org/10.1242/jcs.139246

Liu H, Busch T, Eliason S, Anand D, Bullard S, Gowans LJ, Nidey N, Petrin A, Augustine-Akpan E, Saadi I, Dunnwald M, Lachke SA, Zhu Y, Adeyemo A, Amendt B, Roscioli T, Cornell R, Murray J, Butali A. Exome sequencing provides additional evidence for the involvement ofARHGAP29in Mendelian orofacial clefting and extends the phenotypic spectrum to isolated cleft palate. Birth Defects Research. 2017 Jan 20;109(1):27-37. https://doi.org/10.1002/bdra.23596

Gaczkowska A, Żukowski K, Biedziak B, Hozyasz KK, Wójcicki P, Zadurska M, Budner M, Lasota A, Szponar-Żurowska A, Jagodziński PP, Mostowska A. Association of CDKAL1 nucleotide variants with the risk of non-syndromic cleft lip with or without cleft palate. Journal of Human Genetics. 2018 Feb 5;63(4):397-406. https://doi.org/10.1038/s10038-017-0397-4

Mostowska A, Hozyasz KK, Wójcicki P, Biedziak B, Wesoły J, Sowińska A, Matuszewska-Trojan S, Jagodziński PP. Searching for new genes and loci involved in cleft lip and palate in the Polish population – genome-wide association study. Journal of Medical Science. 2016 Feb;83(3):265-8. https://doi.org/10.20883/medical.78

Ludwig KU, Mangold E, Herms S, Nowak S, Reutter H, Paul A, Becker J, Herberz R, AlChawa T, Nasser E, Böhmer AC, Mattheisen M, Alblas MA, Barth S, Kluck N, Lauster C, Braumann B, Reich RH, Hemprich A, Pötzsch S, Blaumeiser B, Daratsianos N, Kreusch T, Murray JC, Marazita ML, Ruczinski I, Scott AF, Beaty TH, Kramer F, Wienker TF, Steegers-Theunissen RP, Rubini M, Mossey PA, Hoffmann P, Lange C, Cichon S, Propping P, Knapp M, Nöthen MM. Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci. Nature Genetics. 2012 Aug 5;44(9):968-971. https://doi.org/10.1038/ng.2360

Mangold E, Ludwig KU, Birnbaum S, Baluardo C, Ferrian M, Herms S, Reutter H, de Assis NA, Chawa TA, Mattheisen M, Steffens M, Barth S, Kluck N, Paul A, Becker J, Lauster C, Schmidt G, Braumann B, Scheer M, Reich RH, Hemprich A, Pötzsch S, Blaumeiser B, Moebus S, Krawczak M, Schreiber S, Meitinger T, Wichmann H, Steegers-Theunissen RP, Kramer F, Cichon S, Propping P, Wienker TF, Knapp M, Rubini M, Mossey PA, Hoffmann P, Nöthen MM. Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate. Nature Genetics. 2009 Dec 20;42(1):24-26. https://doi.org/10.1038/ng.506

Yuan Q, Blanton SH, Hecht JT. Association of ABCA4 and MAFB with non-syndromic cleft lip with or without cleft palate. American Journal of Medical Genetics Part A. 2011 May 12;155(6):1469-1471. https://doi.org/10.1002/ajmg.a.33940

Fontoura C, Silva RM, Granjeiro JM, Letra A. Further evidence of association of theABCA4gene with cleft lip/palate. European Journal of Oral Sciences. 2012 Oct 15;120(6):553-557. https://doi.org/10.1111/eos.12001

Lennon CJ, Birkeland AC, Nuñez JAP, Su GH, Lanzano P, Guzman E, Celis K, Eisig SB, Hoffman D, Rendon MTG, Ostos H, Chung WK, Haddad J. Association of candidate genes with nonsyndromic clefts in Honduran and Colombian populations. The Laryngoscope. 2012 Jul 2;122(9):2082-2087. https://doi.org/10.1002/lary.23394

Beaty TH, Taub MA, Scott AF, Murray JC, Marazita ML, Schwender H, Parker MM, Hetmanski JB, Balakrishnan P, Mansilla MA, Mangold E, Ludwig KU, Noethen MM, Rubini M, Elcioglu N, Ruczinski I. Confirming genes influencing risk to cleft lip with/without cleft palate in a case–parent trio study. Human Genetics. 2013 Jul 20;132(7):771-781. https://doi.org/10.1007/s00439-013-1283-6

Butali A, Mossey P, Adeyemo W, Eshete M, Gaines L, Braimah R, Aregbesola B, Rigdon J, Emeka C, Olutayo J, Ogunlewe O, Ladeinde A, Abate F, Hailu T, Mohammed I, Gravem P, Deribew M, Gesses M, Adeyemo A, Marazita M, Murray J. Rare functional variants in genome-wide association identified candidate genes for nonsyndromic clefts in the African population. American Journal of Medical Genetics Part A. 2014 Jul 31;164(10):2567-2571. https://doi.org/10.1002/ajmg.a.36691

Letra A, Maili L, Mulliken JB, Buchanan E, Blanton SH, Hecht JT. Further evidence suggesting a role for variation inARHGAP29variants in nonsyndromic cleft lip/palate. Birth Defects Research Part A: Clinical and Molecular Teratology. 2014 Aug 27;100(9):679-685. https://doi.org/10.1002/bdra.23286

Gowans L, Adeyemo W, Eshete M, Mossey P, Busch T, Aregbesola B, Donkor P, Arthur F, Bello S, Martinez A, Li M, Augustine-Akpan E, Deressa W, Twumasi P, Olutayo J, Deribew M, Agbenorku P, Oti A, Braimah R, Plange-Rhule G, Gesses M, Obiri-Yeboah S, Oseni G, Olaitan P, Abdur-Rahman L, Abate F, Hailu T, Gravem P, Ogunlewe M, Buxó C, Marazita M, Adeyemo A, Murray J, Butali A. Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations. Journal of Dental Research. 2016 Jul 20;95(11):1245-1256. https://doi.org/10.1177/0022034516657003

Leslie EJ, 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, Lidral AC, Valencia-Ramirez LC, Lopez-Palacio AM, Valencia DR, Arcos-Burgos M, Czeizel AE, Field LL, Padilla CD, Cutiongco-de la Paz EMC, Deleyiannis F, Christensen K, Munger RG, Lie RT, Wilcox A, Romitti PA, 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, Abate F, Koruyucu M, Seymen F, Ma L, de Salamanca JE, Weinberg SM, Moreno L, Murray JC, Marazita ML. A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13. Human Molecular Genetics. 2016 Mar 30;:ddw104. https://doi.org/10.1093/hmg/ddw104

Kondo S, Schutte BC, Richardson RJ, Bjork BC, Knight AS, Watanabe Y, Howard E, Ferreira de Lima RL, Daack-Hirsch S, Sander A, McDonald-McGinn DM, Zackai EH, Lammer EJ, Aylsworth AS, Ardinger HH, Lidral AC, Pober BR, Moreno L, Arcos-Burgos M, Valencia C, Houdayer C, Bahuau M, Moretti-Ferreira D, Richieri-Costa A, Dixon MJ, Murray JC. Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. Nature Genetics. 2002 Sep 3;32(2):285-289. https://doi.org/10.1038/ng985

Uslu VV, Petretich M, Ruf S, Langenfeld K, Fonseca NA, Marioni JC, Spitz F. Long-range enhancers regulating Myc expression are required for normal facial morphogenesis. Nature Genetics. 2014 May 25;46(7):753-758. https://doi.org/10.1038/ng.2971

Paul B, Palmer K, Sharp J, Pratt C, Murray S, Dunnwald M. ARHGAP29 Mutation Is Associated with Abnormal Oral Epithelial Adhesions. Journal of Dental Research. 2017 Aug 17;96(11):1298-1305. https://doi.org/10.1177/0022034517726079

Leslie E, Taub M, Liu H, Steinberg K, Koboldt D, Zhang Q, Carlson J, Hetmanski J, Wang H, Larson D, Fulton R, Kousa Y, Fakhouri W, Naji A, Ruczinski I, Begum F, Parker M, Busch T, Standley J, Rigdon J, Hecht J, Scott A, Wehby G, Christensen K, Czeizel A, Deleyiannis F, Schutte B, Wilson R, Cornell R, Lidral A, Weinstock G, Beaty T, Marazita M, Murray J. Identification of Functional Variants for Cleft Lip with or without Cleft Palate in or near PAX7, FGFR2, and NOG by Targeted Sequencing of GWAS Loci. The American Journal of Human Genetics. 2015 Mar;96(3):397-411. https://doi.org/10.1016/j.ajhg.2015.01.004

Weng J, Mata NL, Azarian SM, Tzekov RT, Birch DG, Travis GH. Insights into the Function of Rim Protein in Photoreceptors and Etiology of Stargardt's Disease from the Phenotype in abcr Knockout Mice. Cell. 1999 Jul;98(1):13-23. https://doi.org/10.1016/s0092-8674(00)80602-9

Burke TR, Tsang SH. Allelic and phenotypic heterogeneity inABCA4mutations. Ophthalmic Genetics. 2011 Apr 21;32(3):165-174. https://doi.org/10.3109/13816810.2011.565397

Leslie EJ, Mansilla MA, Biggs LC, Schuette K, Bullard S, Cooper M, Dunnwald M, Lidral AC, Marazita ML, Beaty TH, Murray JC. Expression and mutation analyses implicate ARHGAP29 as the etiologic gene for the cleft lip with or without cleft palate locus identified by genome-wide association on chromosome 1p22. Birth Defects Research Part A: Clinical and Molecular Teratology. 2012 Sep 24;94(11):934-942. https://doi.org/10.1002/bdra.23076

Zucchero TM, Cooper ME, Maher BS, Daack-Hirsch S, Nepomuceno B, Ribeiro L, Caprau D, Christensen K, Suzuki Y, Machida J, Natsume N, Yoshiura K, Vieira AR, Orioli IM, Castilla EE, Moreno L, Arcos-Burgos M, Lidral AC, Field LL, Liu Y, Ray A, Goldstein TH, Schultz RE, Shi M, Johnson MK, Kondo S, Schutte BC, Marazita ML, Murray JC. Interferon Regulatory Factor 6 (IRF6) Gene Variants and the Risk of Isolated Cleft Lip or Palate. New England Journal of Medicine. 2004 Aug 19;351(8):769-780. https://doi.org/10.1056/nejmoa032909

Kardassis D, Murphy C, Fotsis T, Moustakas A, Stournaras C. Control of transforming growth factor β signal transduction by small GTPases. FEBS Journal. 2009 Jun;276(11):2947-2965. https://doi.org/10.1111/j.1742-4658.2009.07031.x

Schlessinger K, Hall A, Tolwinski N. Wnt signaling pathways meet Rho GTPases. Genes & Development. 2009 Feb 1;23(3):265-277. https://doi.org/10.1101/gad.1760809

Chandrasekharan D, Ramanathan A. Identification of a novel heterozygous truncation mutation in exon 1 of ARHGAP29 in an Indian subject with nonsyndromic cleft lip with cleft palate. European Journal of Dentistry. 2014 Oct;8(4):528-532. https://doi.org/10.4103/1305-7456.143637

Wen Y, Lu Q. Risk prediction models for oral clefts allowing for phenotypic heterogeneity. Frontiers in Genetics. 2015 Aug 13;6. https://doi.org/10.3389/fgene.2015.00264

Rahimov F, Marazita ML, Visel A, Cooper ME, Hitchler MJ, Rubini M, Domann FE, Govil M, Christensen K, Bille C, Melbye M, Jugessur A, Lie RT, Wilcox AJ, Fitzpatrick DR, Green ED, Mossey PA, Little J, Steegers-Theunissen RP, Pennacchio LA, Schutte BC, Murray JC. Disruption of an AP-2α binding site in an IRF6 enhancer is associated with cleft lip. Nature Genetics. 2008 Oct 5;40(11):1341-1347. https://doi.org/10.1038/ng.242

Savastano C, Brito L, Faria Á, Setó-Salvia N, Peskett E, Musso C, Alvizi L, Ezquina S, James C, GOSgene, Beales P, Lees M, Moore G, Stanier P, Passos-Bueno M. Impact of rare variants inARHGAP29to the etiology of oral clefts: role of loss-of-functionvsmissense variants. Clinical Genetics. 2016 Jul 26;91(5):683-689. https://doi.org/10.1111/cge.12823

Carlson JC, Nidey NL, Butali A, Buxo CJ, Christensen K, Deleyiannis FW, Hecht JT, Field LL, Moreno-Uribe LM, Orioli IM, Poletta FA, Padilla C, Vieira AR, Weinberg SM, Wehby GL, Feingold E, Murray JC, Marazita ML, Leslie EJ. Genome-wide interaction studies identify sex-specific risk alleles for nonsyndromic orofacial clefts. Genetic Epidemiology. 2018 Sep 11;42(7):664-672. https://doi.org/10.1002/gepi.22158

Carlson JC, Taub MA, Feingold E, Beaty TH, Murray JC, Marazita ML, Leslie EJ. Identifying Genetic Sources of Phenotypic Heterogeneity in Orofacial Clefts by Targeted Sequencing. Birth Defects Research. 2017 Aug 1;109(13):1030-1038. https://doi.org/10.1002/bdr2.23605

Wehby G, Murray J. Folic acid and orofacial clefts: a review of the evidence. Oral Diseases. 2010 Jan;16(1):11-19. https://doi.org/10.1111/j.1601-0825.2009.01587.x

Hackshaw A, Rodeck C, Boniface S. Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls. Human Reproduction Update. 2011 Jul 11;17(5):589-604. https://doi.org/10.1093/humupd/dmr022

Published

2020-06-26

How to Cite

1.
Dąbrowska J, Biedziak B, Lasota A, Jagodziński PP, Mostowska A. Role of ARHGAP29 nucleotide variants in the etiology of non-syndromic cleft lip with or without cleft palate. JMS [Internet]. 2020Jun.26 [cited 2021Apr.14];89(2):e414. Available from: https://jms.ump.edu.pl/index.php/JMS/article/view/414

Issue

Section

Original Papers