【作者】 申屠形超；

【导师】 姚克；

【作者基本信息】 浙江大学 ， 眼科学， 2005， 博士

【摘要】 白内障是全球首要致盲眼病。其中,先天性白内障是一种临床常见的儿童眼病,发病率为6/10000～6/1000。在天津、上海和北京等地的流行病学调查发现,约22～30%的盲童因此而致盲,占失明原因的第二位。目前手术仍是先天性白内障的主要治疗方法,但由于无法早期检查婴幼儿视力,常常造成手术时机的延误,而且儿童白内障手术疗效欠佳(术后后发障发生率几乎为100%),故有许多儿童因本病而导致不可逆转的弱视。此外,因基因突变引起的先天性白内障多为单基因显性遗传,患者后代的发病率为50%左右,具有很高的遗传性,严重影响了下一代的健康。先天性白内障的防治任重而道远,防治先天性白内障造成的视力障碍是世界卫生组织2020年消灭可避免视力下降的主要目标之一。 环境因素和遗传因素是先天性白内障的两大病因,大约25%的先天性白内障与遗传缺陷有关。随着分子遗传学技术的发展,遗传因素是近年来研究的热点,越来越多的先天性更多还原

【Abstract】 Cataracts are a leading cause of blindness worldwide and congenital cataracts are a common eye disease in children, which has the incident rate of 6/1000~6/l0000. In the epidemiological study in Beijing, Tianjing and Shanghai, it is the secondary cause of all blindness in children, which is nearly 22~30%. Because these congenital cataracts result in cloudy imaging onto the retina, the abnormal development of visual cortical synaptic connections results in amblyopia, which causes affected children irreversible visual loss if without suitable intervention. The gene mutation is the most common reason and the offspring also have the risk to have the same disease. Prevention of visual impairment due to congenital cataract is an important component of the World Health Organization’s (WHO) international program for the elimination of avoidable blindness by 2020.Both environmental factor and genetic factor can cause the congenital cataract. About 25%of all congenital cataracts are inherited. With the development of advanced molecular biological techniques, more and more congenital cataract disease-associated genes have been identified, including 1) crystalline genes, which changing the structure and array of lens fiber cells, i.e. <xA crystalline gene; 2) membrane protein genes, which affecting the information transmission between the lens fiber cells, i.e. connexin gene; 3) cytoskeletal protein genes, which determined the structural framework of lens cells, i.e. beaded filament structural protein 2 gene; 4) accommodation genes, which interforencing the lens development, i.e. homeobox gene 3; 5) unknown functional protein genes, i.e. lens intrinsic membrane protein 2 gene.In general, congenital cataracts are bilateral and characterized by the location and structure of the opacities, which include shape, size, color and the presence or absence of refractivity. However, phenotypic variability has been documented among and within families, whereby identical mutations can result in different phenotypes. And the identical cataracts have also been mapped to different loci. There are two major methods used in cataract candidate disease-associated gene research: one is basing on major functional protein associated with cataractgenesis, mapping the candidate gene location by hybridization; the other is mapping the locus for congenital cataract in typical family using genomic genescan, candidate gene linkage analysis and candidate gene screening to identifying the disease-associated gene.Here, we studied a large, four-generation Chinese family containing members affected by congenital cataract of special fasciculiform and all affected family members showed a special fasciculiform cataract characterized by corroliform opacification, which included embryonic and fetal nuclei, and needl-like or fiberglasslike opacity projecting in different directions from thecentral zone with the radially oriented metal-like refractivity. Autosomal dominant inheritance of the congenital cataract was demonstrated by chi square and Single Method test. We are going to study the ultrastructure and the candidate disease-associated gene of this special fasciculiform congenital cataract, clarifying the congenital cataract mechanisms in human. Informed consent in accordance with the Declaration of Helsinki and Zhejiang Institutional Review Board approval was obtained from all participants. Informed consent was also obtained from the subjects after explanation of the nature and possible consequences of the study.Part I The special fasciculiform congenital cataract familyThirty-seven individuals participated in the study: 13 affected individuals and 24 unaffected individuals of whom 12 were spouses. Affected status was determined by a history of cataract extraction or ophthalmologic examination, which including slit-lamp examination under dilated pupils, visual acuity testing and fundus examination. The cataract phenotype of the patients who had had cataract extraction was learned from the history records. All affected family members showed a special fasciculifor更多还原