【作者】 殷亚男；

【导师】 赵鲁杭；

【作者基本信息】 浙江大学 ， 生物化学与分子生物学， 2006， 硕士

【摘要】 先天性小眼球(congenital microphthalmia,CMIC)是一种先天发育异常性眼科疾病,主要表现为眼球前后径小于正常范围,睑裂窄,眼眶小,眼球深陷于眼眶内。患者视力通常较差,且难以治疗。先天性小眼球有多种类型:仅表现为眼球体积小,不伴有其他异常者称为单纯性小眼球,较少见;多数先天性小眼球伴有眼部其他畸形,如前节发育不全,先天性白内障,脉络膜视网膜缺损,视网膜发育不良,视神经缺损等:最严重的类型是先天性无眼球。该病散发病例居多,也有家族遗传的报道,遗传方式有常染色体显性遗传(autosomal dominant,AD),常染色体隐性遗传(autosomal recessive,AR)和X连锁隐性遗传(X-linked recessive,XR)。目前的研究认为与先天性小眼球相关的致病基因或位点有:MITF、SOX2、PAX6、MCOP和NNO2等。 本研究拟采用基因扫描技术,通过连锁分析对一个先天性小眼球家系进行疾病相关基因的定位研究。研究对象是一个来自浙江的五代常染色体显性遗传先天性小眼球家系。从该家系8名患者和11名正常成员的外周静脉血提取基因组DNA,根据已报道的与先天性小眼球有关的5个位点(MITF、SOX2、PAX6、MCOP和NNO2),在3、11、14和15号染色体上选取了14个微卫星标记,以荧光标记引物的聚合酶链反应(PCR)扩增目的片段,用ABI377 DNA遗传分析仪对该家系进行基因扫描和基因分型,通过Linkage软件包对基因分型结果更多还原

【Abstract】 Congenital microphthalmia is a developmental ocular malformation characterized by a small eye, shorted axial length, narrow palpebral fissure, small fossa orbitalis. Congenital microphthalmia can result in severe visual consequences. Congenital microphthalmia have different clinical manifestations, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Nanophthalmos is a relatively rare condition characterized by a small eye in the absence of any systemic abnormalities. Congenital microphthalmia is frequently associated with other ocular abnormalities, including anterior segment dysgenesis, cataract, chorioretinal coloboma, retinal dysplasia and optic-nerve coloboma. Anophthalmos is extreme form of microphthalmos. Although most cases of microphthalmia are sporadic, a few family with autosomal dominant, autosomal recessive, and X-linked recessive inheritance of the trait have been reported. The associated genes for congenital microphthalmia have been mapped on several loci: MITF S0X2 PAX6 MCOP NN02 and so on. The additional locus remains to be identificated.Research had been performed on a Chinese pedigree of autosomal dominantcongenital microphthalmia through genescan and linkage analysis to investigate the location of the disease-causing gene associated with the family. We had identified a five generations pedigree of autosomal dominant congenital microphthalmia came from zhejiang province. Genomic DNA was extracted from peripheral blood samples of 8 affected and 11 unaffected family members. According to five loci reported previously (MITF, SOX2, PAX6, MCOP and NN02), 14 microsatellite markers on chromosome 3, 11 14 15 were used as genetic markers and were amplified by PCR (polymerase chain reaction) with fluorescence labeled primers. Genome screening and genotyping were conducted by ABI377 DNA sequencer in this microphthalmia family and linkage analysis was performed with LINKAGE software package.The LOD scores less than - 2 at all 14 microsatellite markers indicated that there was no linkage between these markers and the disease locus in this microphthalmia family. The gene responsible for microphthalmia in this family is distinct from the five reported loci. Microphthalmia in this family may be resulted from defects in a new developmental gene which is essential in eye development.更多还原