Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome.

Autor: Alade AA; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA.; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA, USA., Buxo-Martinez CJ; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico., Mossey PA; Department of Orthodontics, University of Dundee, Dundee, United Kingdom., Gowans LJJ; Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Eshete MA; School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia., Adeyemo WL; Department of Oral and Maxillofacial Surgery, University of Lagos, Lagos, Nigeria., Naicker T; School of clinical medicine, KwaZulu-Natal University, Durban, South Africa., Awotoye WA; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA., Adeleke C; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA., Busch T; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA., Toraño AM; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico., Bello CA; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico., Soto M; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico., Soto M; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico., Ledesma R; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico., Marquez M; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico., Cordero JF; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico., Lopez-Del Valle LM; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico., Salcedo MI; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico., Debs N; Dental and Craniofacial Genomics Core, University of Puerto Rico School of Dental Medicine, San Juan, Puerto Rico., Li M; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA., Petrin A; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA., Olotu J; Department of Anatomy, University of Port Harcourt, Port Harcourt, Nigeria., Aldous C; School of clinical medicine, KwaZulu-Natal University, Durban, South Africa., Olutayo J; Department of Oral and Maxillofacial Surgery, University of Lagos, Lagos, Nigeria., Ogunlewe MO; Department of Oral and Maxillofacial Surgery, University of Lagos, Lagos, Nigeria., Abate F; School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia., Hailu T; School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia., Muhammed I; School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia., Gravem P; School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia., Deribew M; School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia., Gesses M; School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia., Hassan M; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA., Pape J; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA., Adeniyan OA; NHS Foundation Trust, (Queens Hospital, Burton-On-Trent), Staffordshire, United Kingdom., Obiri-Yeboah S; Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Arthur FKN; Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Oti AA; Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Olatosi O; Department of Child Dental Health, University of Lagos, Nigeria., Miller SE; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA., Donkor P; Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, Ghana., Dunnwald MM; Department of Anatomy, University of Iowa, Iowa City, IA, USA., Marazita ML; Oral Biology, Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA., Adeyemo AA; National Human Genomic Research Institute, Bethesda, MD, USA., Murray JC; Department of Pediatrics, University of Iowa, Iowa City, IA, USA., Butali A; Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, USA.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2020 Aug; Vol. 8 (8), pp. e1355. Date of Electronic Publication: 2020 Jun 17.
DOI: 10.1002/mgg3.1355
Abstrakt: Background: The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well-organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA-binding (exon 3, 4) or protein-binding domains (exon 7-9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico.
Methods: We used PubMed with the search terms; "Van der Woude syndrome," "Popliteal pterygium syndrome," "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants.
Results: Twenty-one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7-9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein-binding domain (exon 7-9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*).
Conclusion: Mutations in the protein and DNA-binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes.
(© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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