Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate
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Date
2018-05-01
Authors
Gowans, L.J.J.
Oseni, G.
Mossey, P.A.
Adeyemo, W.L.
Eshete, M.A.
Busch, T.D.
Donkor, P.
Obiri-Yeboah, S.
Plange-Rhule, G.
Oti, A.A.
Journal Title
Journal ISSN
Volume Title
Publisher
SAGE JOURNALS
Abstract
OBJECTIVE:
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.
PATIENTS AND METHOD:
We 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.
RESULTS:
The 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.
CONCLUSION:
Our 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.
Description
Staff publications
Keywords
Sub-Saharan Africa , GREM1 gene , Mutation , Cleft lip and palate , DNA sequencing , Research Subject Categories::ODONTOLOGY
Citation
Gowans LJJ, Oseni G, Mossey PA, Adeyemo WL, Eshete MA, Busch TD, Donkor P, Obiri-Yeboah S, Plange-Rhule G, Oti AA, Owais A, Olaitan PB, Aregbesola BS, Oginni FO, Bello SA, Audu R, Onwuamah C, Agbenorku P, Ogunlewe MO, Abdur-Rahman LO, Marazita ML, Adeyemo AA, Murray JC, Butali A. Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate. Cleft Palate Craniofac J. 2018 May;55(5):736-742.