Molecular Genetic Etiology of Craniosynostosis among Ghanaians (MoGECaG)

颅缝融合是仅次于口面部裂(OFC)的第二大常见的头面部出生缺陷。 2000年影响1至2,500名活产儿。这种情况有多因素的病因，既有遗传因素 而环境风险因素起着至关重要的作用。约90%的颅骨融合症病例 是非家族性的，大约15%的病例是综合征，表现为其他颅外症状 约180个综合征中的异常。缺陷源于一种或多种过早融合。 颅缝最终导致颅骨异常生长和颅内压升高。就像 其他颅面先天缺陷，颅缝早闭具有终生的心理社会、审美、临床和 对受影响的个人和家庭造成经济负担。就像许多基因研究中常见的那样， 撒哈拉以南非洲人在旨在阐明 颅缝早闭的病理生理学研究。尽管如此，亚种的巨大遗传多样性- 撒哈拉非洲基因组，再加上其较短的单倍型区块，提供了巨大的潜力 颅缝早闭的病因学变异和/或基因发现。据我们所知，我们是 提出了有史以来第一个关于撒哈拉以南非洲人颅缝融合症的基因研究项目。 这一合作研究项目的具体目标有三个：(A)建设研究能力 在加纳的颅缝融合症方面，长期目标是推广到其他非洲国家，(B)进行 非综合征性颅缝早闭患者与对照组的基因表达差异 (C)对症状性和非症状性颅脑融合病例进行外显子全序列测定。 具体目标1将磨练加纳队在颅缝融合方面的知识和技能 具体目标2和3将在加纳建立研究基础设施。 这些都是加纳团队在#年过渡到独立调查人员所必需的。 颅缝融合症的未来研究。这些具体目标将通过 三位首席研究人员的合作努力：Jephthah Joojo Gowans勋爵和 加纳夸梅·恩克鲁马科技大学的所罗门·奥比里-耶博阿和 迈克尔·L·坎宁安，西雅图儿童颅面中心和加州大学 美国华盛顿。Peter Donkor博士，口腔颌面外科医生，教育家和研究人员， 威尔担任该项目的顾问。拟议中的项目有可能揭示 人群特有的遗传变异和/或基因，可能使个人容易患上 颅骨融合症。该项目还具有翻译潜力，因为它将识别高危家庭-a 遗传咨询的必要性。这在中低收入人群中尤为重要 像加纳这样的国家，几乎不存在基因测试和新生儿筛查。

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.