Identification and characterisation of novel genes for congenital cataract

白内障是世界范围内导致失明的主要原因。该术语描述了可能导致视力障碍的透镜混浊。先天性白内障（出生时就存在）比年龄相关性白内障不太常见，但对视力的终身影响可能是严重的，三分之一的患者仍然是合法失明。晚期并发症如无晶状体性青光眼可能致盲。我们已经证明先天性白内障通常是遗传的，并在过去5年中在澳大利亚东南部进行了一项基于人群的研究，以确定致病基因。大量的家庭参与了这项研究，在识别白内障基因突变和了解这些突变对患者预后的影响方面取得了坚实的进展。我们最近在一个患有白内障、智力迟钝和牙齿问题综合征的澳大利亚大家庭中发现了一种新的基因。这种综合征，被称为Nance-Horan综合征，最初于30年前在澳大利亚被描述，我们与原始家庭合作寻找确切的基因。我们已经知道这个基因在其他家族中会引起同样的综合征，在这个项目中，我们将研究它是否会引起没有其他特征的白内障或没有白内障的智力迟钝。我们将进行一系列的实验来了解这种基因的作用以及它是如何导致这种疾病的。我们还选择了其他3个非常有趣的先天性白内障家族进行进一步研究，因为我们已经知道或强烈怀疑它们将使我们能够进一步确定白内障的新基因，在一个病例中是智力迟钝。我们在其他疾病方面的工作表明，了解严重年轻发病病例的基因可以为年龄相关形式的原因提供有价值的线索，并可能在未来实现预防和治疗全球失明最常见原因的新方法。

Cataracts are the leading cause of blindness worldwide. The term describes a clouding of the lens which may lead to visual impairment. Congenital cataracts (present at birth) are less common than age-related cataract but the lifelong impact on vision can be severe, with a third of patients remaining legally blind. Late complications such as aphakic glaucoma may be blinding. We have shown that congenital cataracts are often inherited and have performed a population-based study in South-Eastern Australia over the past 5 years to determine the causative genes. A large number of families have been involved in the study and solid progress has been made in identifying mutations in cataract genes and understanding what effect these may have on the patient's prognosis. We have recently identified a new gene in a large Australian family with a syndrome of cataract, mental retardation and teeth problems. This syndrome, known as Nance-Horan syndrome was originally described in Australia 30 years ago and we have worked with the original family to find the exact gene responsible. We already know that this gene causes the same syndrome in other families and in this project we will examine whether it can cause cataract without the other features or mental retardation without cataract. We will perform a series of experiments to learn what this gene does and how it causes the disease. We have also selected 3 other very interesting families with congenital cataracts for further study as we either know already or strongly suspect that they will enable us to identify further new genes for cataract, and in one case mental retardation. Our work in other diseases indicates that understanding the genes in severe young onset cases can give valuable clues to the causes of age-related forms and may in the future enable new ways to prevent and treat the commonest cause of worldwide blindness.