Molecular Genetic Etiology of Craniosynostosis among Ghanaians (MoGECaG)

Kwame Nkrumah University/Science/Tech, Kumasi

Investigators

Abstract

Craniosynostosis is the second most common craniofacial birth defect after orofacial clefts (OFCs) affecting 1 in 2000 to 2,500 live births. The condition has a multifactorial etiology, with both genetic and environmental risk factors playing crucial roles. Approximately 90% of craniosynostosis cases are non-familial and about 15% of cases are syndromic, presenting with other extra-cranial anomalies in about 180 syndromes. The defect emanates from premature fusion of one or more cranial sutures culminating in abnormal skull growth and increased intracranial pressure. Just like other craniofacial birth defects, craniosynostosis has life-long psychosocial, esthetic, clinical and financial burden on affected individuals and families. As is common with many genetic studies, sub-Saharan African is conspicuously missing in genetic etiologic studies aimed at elucidating the pathophysiology of craniosynostosis. This notwithstanding, the vast genetic diversity of the sub- Saharan African genome, coupled with its shorter haplotype block offer a great potential for etiologic variant and/or gene discovery for craniosynostosis. To the best of our knowledge, we are proposing the first ever genetic research project on craniosynostosis among sub-Saharan Africans. The specific aims of this collaborative research project are threefold: (a) to build research capacity in craniosynostosis in Ghana, with a long term goal to extend to other African countries, (b) to carry out differential gene expression between nonsyndromic craniosynostosis cases and controls, and (c) to carry out whole exome sequencing of syndromic and nonsyndromic craniosynostosis cases. Specific aim 1 will hone the knowledge and skill of the Ghanaian team in craniosynostosis research whereas specific aims 2 and 3, inter alia, will build research infrastructure in Ghana. These are necessary for the Ghanaian team to transition into independent investigators in craniosynostosis research in the future. These specific aims will be achieved through the collaborative efforts of three Principal Investigators: Drs. Lord Jephthah Joojo Gowans and Solomon Obiri-Yeboah of Kwame Nkrumah University of Science and Technology, Ghana, and Michael L. Cunningham of Seattle Children?s Craniofacial Center and the University of Washington, USA. Dr. Peter Donkor, an Oral and Maxillofacial Surgeon, educator and researcher, will serves as the consultant on the project. The proposed project has the potential of revealing population-specific genetic variants and/or genes that may predispose individuals to craniosynostosis. The project also has translational potential as it will identify high risk families ? a necessity for genetic counselling. This is particularly important in a Lower and Middle Income Country like Ghana, where genetic tests and newborn screening is almost non-existent.