Clinical and Genetic Analysis of Microphthalmia

该项目旨在了解综合征性小眼炎的临床和分子基础。这种疾病包括无眼症或小眼症(小眼或无眼失明)、智力低下和骨骼异常。我们已经确定了一个受Lenz小眼症影响的大家族，并将该基因定位到X染色体的短臂上。这一结果令人惊讶，因为另一个患有这种疾病的家庭映射到X染色体的长臂上。这意味着Lenz小眼炎可能是两种疾病的混合体。我们已经使用位置克隆来分离在这种情况下改变的基因，这被称为BCOR(BCL-6共抑制物)。此外，我们还发现，该基因的突变也会导致眼面部心脏-牙齿综合征。我们目前正在评估这些突变在斑马鱼模型系统中的功能后果。

The project seeks to understand the clinical and molecular basis of syndromic microphthalmia. This disorder comprises anophthalmia or microphthalmia (small or absent eyes with blindness), mental retardation, and skeletal anomalies. We have identified a large family affected by Lenz Microphthalmia and have mapped the gene to the short arm of the X chromosome. This result is surprising because another family with this disorder maps to the long arm of the X chromosome. This means that Lenz microphthalmia is probably an amalgam of two disorders. We have used positional cloning to isolate the gene that is altered in the condition, which is called BCOR (BCL-6 co-repressor). In addition, we have discovered that mutations in this gene also cause the Oculo-facio-cardi-dental syndrome. We are currently assessing the functional consequence of these mutations in a zebrafish model system.