Genetics of Moebius syndrome and other congenital facial weakness disorders

莫比斯综合症和其他先天性面部无力疾病的遗传学

• 批准号: 8750719
• 负责人: FRANCIS S. COLLINS
• 金额: $ 63.6万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8750719
• 关键词: Affect; Birth; Brain Stem; Candidate Disease Gene; Caring; Case Study; Cell Nucleus; Clinical; Complex; Cranial Nerves; Deformity; Development; Diagnosis; Disease; Environmental Risk Factor; Etiology; Eye; Face; Facial nerve structure; Facial paralysis; Family; Family Study; Family member; Functional disorder; Gene Mutation; Genes; Genetic; Genetic Variation; Germ-Line Mutation; Goals; Heterogeneity; Impairment; Incidence; Individual; Limb structure; Mechanics; Operative Surgical Procedures; Parents; Pathogenesis; Pathway interactions; Population; Publishing; Siblings; Somatic Mutation; Subgroup; Susceptibility Gene; Syndrome; Variant; Vascular blood supply; base; clinical phenotype; craniofacial; exome sequencing; member; prenatal environmental exposure; racial and ethnic; social

We have completed exome sequencing of individuals from four families, which have at least one member affected with Moebius syndrome. Each family unit consists of the affected individual(s), non-affected parents, and in some cases, non-affected siblings. We identified a few candidate genes (1-3) per family that have variants segregating with Moebius syndrome (i.e. in affected family members and not in the non-affecteds). The genes identified do not overlap with any of the published candidate genes. Notably, we have not identified candidate genes in common across two or more of the four families studied. It is clear that interrogating a larger number of such families will be needed to increase the chance of finding common genes or genes in common pathways. Furthermore, the ability to assess more homogeneous subgroups of affected individuals based on detailed clinical phenotyping will be invaluable given the complexity and heterogeneity of this disorder with regards to both genetic and potential environmental factors.

我们已经完成了来自四个家庭的个体的外显子组测序，这至少有一个患有Moebius综合征的成员。每个家庭单位由受影响的个体，不受影响的父母组成，在某些情况下是未受影响的兄弟姐妹。我们确定了每个家族的一些候选基因（1-3），这些基因具有与Moebius综合征分离的变体（即受影响的家庭成员而不是在未受到影响的家庭成员中）。所鉴定的基因不会与任何已发表的候选基因重叠。值得注意的是，我们尚未确定在研究的四个家庭中的两个或多个家庭中共有的候选基因。显然，需要审问大量此类家庭，以增加在常见途径中找到常见基因或基因的机会。此外，鉴于这种疾病在遗传和潜在的环境因素方面，基于详细的临床表型评估受影响个体的更均匀亚组的能力将是无价的。