Journal article
Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate
The Cleft palate-craniofacial journal, Vol.55(5), pp.736-742
05/2018
DOI: 10.1177/1055665618754948
PMCID: PMC6081638
PMID: 29489415
Abstract
Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate.\nWe resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature.\nThe novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene.\nOur study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P.
Details
- Title: Subtitle
- Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate
- Creators
- Lord Jephthah Joojo Gowans - 1 Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, GhanaGaniyu Oseni - 2 Department of Plastic Surgery, Ladoke Akintola University of Science and Technology, Osogbo, NigeriaPeter A Mossey - 3 Department of Orthodontics, University of Dundee, Dundee, United KingdomJeffrey C Murray - 6 Department of Pediatrics, University of Iowa, Iowa City, IA, USAAzeez Butali - 15 Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USAWasiu Lanre Adeyemo - 4 Department of Oral and Maxillofacial Surgery, University of Lagos, Lagos, NigeriaMekonen A Eshete - 5 Addis Ababa University, School of Public Health, Addis Ababa, EthiopiaTamara D Busch - 6 Department of Pediatrics, University of Iowa, Iowa City, IA, USAPeter Donkor - 1 Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, GhanaSolomon Obiri-Yeboah - 1 Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, GhanaGyikua Plange-Rhule - 1 Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, GhanaAlexander A Oti - 1 Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, GhanaArwa Owais - 7 Department of Pediatric Dentistry, University of Iowa, Iowa City, IA, USAPeter B Olaitan - 2 Department of Plastic Surgery, Ladoke Akintola University of Science and Technology, Osogbo, NigeriaBabatunde S Aregbesola - 8 Department of Oral and Maxillofacial Surgery, Obafemi Awolowo University, Ile-Ife, NigeriaFadekemi O Oginni - 8 Department of Oral and Maxillofacial Surgery, Obafemi Awolowo University, Ile-Ife, NigeriaSeidu A Bello - 9 State House Clinic, Abuja, NigeriaRosemary Audu - 10 Department of Virology, Nigerian Institute of Medical Research, Lagos, NigeriaChika Onwuamah - 10 Department of Virology, Nigerian Institute of Medical Research, Lagos, NigeriaPius Agbenorku - 1 Cleft Clinic, Komfo Anokye Teaching Hospital and Kwame Nkrumah University of Science and Technology, Kumasi, GhanaMobolanle O Ogunlewe - 4 Department of Oral and Maxillofacial Surgery, University of Lagos, Lagos, NigeriaLukman O Abdur-Rahman - 11 Division of Pediatric Surgery, Department of Surgery, University of Ilorin, Ilorin, NigeriaMary L Marazita - 13 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USAA A Adeyemo - 14 National Human Genome Research Institute, Bethesda, MD, USA
- Resource Type
- Journal article
- Publication Details
- The Cleft palate-craniofacial journal, Vol.55(5), pp.736-742
- DOI
- 10.1177/1055665618754948
- PMID
- 29489415
- PMCID
- PMC6081638
- NLM abbreviation
- Cleft Palate Craniofac J
- ISSN
- 1055-6656
- eISSN
- 1545-1569
- Publisher
- United States
- Grant note
- R37 DE008559 / NIDCR NIH HHS\nR00 DE022378 / NIDCR NIH HHS\nR01 DE016148 / NIDCR NIH HHS
- Language
- English
- Date published
- 05/2018
- Academic Unit
- Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984066097602771
Metrics
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