1、眼睛单基因疾病的早期诊断与遗传咨询 杨正林 电子科技大学医学院 四川省医学科院 /四川省人民医院 中国科学院四川转化医学研究医院 1. 遗传物质的存在 2. 遗传与分离规律 3. 显性遗传和隐性遗传规律 http:/en.wikipedia.org/wiki/ http:/en.wikipedia.org/wiki/ X-连锁 遗传规律 核酸（ nuclein（ now nucleic acids）的发现 http:/en.wikipedia.org/wiki/ 核苷酸碱基（ A T G C U)的发现 http:/en.wikipedia.org/wiki/ 遗传物质 DNA与基因和染色体的
2、联系（ 1944） DNA结构 DNA测序 Human Genome Project Completed in 2003, the Human Genome Project (HGP) was a 13-year project coordinated by the U.S. Department of Energy and the National Institutes of Health. During the early years of the HGP, the Wellcome Trust (U.K.) became a major partner; additional contr
3、ibutions came from Japan, France, Germany, China, and others. identify all the approximately 20,000-25,000 genes in human DNA, determine the sequences of the 3 billion chemical base pairs that make up human DNA, store this information in databases, improve tools for data analysis, transfer related t
4、echnologies to the private sector, and address the ethical, legal, and social issues (ELSI) that may arise from the project. Though the HGP is finished, analyses of the data will continue for many years. 测 序花 费 直 线 下降 单 基因疾病 （polygenic diseases) 多基因疾病 (polygenic diseases) 光信号 不可逆的 视力下降甚至失明 - 3 - 化学信
5、号 基因突变 视觉形成 http:/www.siggraph.org/education/materials/HyperVis/vision/eyebrain.htm http:/webvision.med.utah.edu RPE 眼科 临 床 检查 病人主述，症状，体征， 视 力，眼底（ 镜 ，照相），血管造影，眼 压 ，OCT，房角，视 野， 电 生理（ ERG)，角膜，眼 轴 ，病理，房水， CT，MRI，实验 室 检查 （血常规 ，生化，免疫，微生物等） 基因 诊 断 Ptosis(眼 睑 下垂） http:/en.wikipedia.org/wiki/Ptosis_(eyelid)
6、 omim A number sign (#) is used with this entry because the blepharophimosis-ptosis-intellectual disability syndrome (BPIDS) is caused by heterozygous mutation in the UBE3B gene (608047) on chromosome 12q23. Most cases are in syndromes Strabismus(斜 视 ） http:/zh.wikipedia.org/wiki and OMIM Overall, e
7、sotropia is more common than exotropia. 先天性眼外肌纤维化 congenital fibrosis of extraocular muscles-1 (CFEOM1) is caused by heterozygous mutation in the KIF21A gene (608283) on chromosome 12q12 CFEOM2 (602078), an autosomal recessive disorder caused by mutation in the ARIX gene (602753) on chromosome 11q13
8、, is characterized by bilateral ptosis with eyes fixed in an exotropic position. Nystagmus(眼球震 颤 ) A number sign (#) is used with this entry because of evidence that childhood-onset neurodegeneration with optic atrophy (NDGOA) is caused by homozygous mutation in the UCHL1 gene (191342) on chromosome
9、 4p14. One such family has been reported. OMIM A form of autosomal recessive nonsyndromic deafness designated DFNB84A (613391), which also maps to chromosome 12q21, is caused by mutation in the PTPRQ gene (603317). most cases are in syndromes A number sign (#) is used with this entry because of evid
10、ence that X-linked congenital nystagmus-1 (NYS1) and infantile periodic alternating nystagmus (XIPAN) are caused by mutation in the FERM domain-containing-7 gene (FRMD7; 300628) on chromosome Xq26. http:/webvision.med.utah.edu Corneal Dystrophy Fifteen genes out of nineteen loci Klintworth et al. Or
11、phanet Journal of Rare Disease 2009 Klintworth et al. Orphanet Journal of Rare Disease 2009 Klintworth et al. Orphanet Journal of Rare Disease 2009 Klintworth et al. Orphanet Journal of Rare Disease 2009 A B C D 共聚焦显微镜显示角膜呈糜烂状 格子状角膜营养变性 (lattice corneal dystrophy )-TGFBI (exon4:c.C370T:p.R124C) 先天性无虹膜伴晶体脱位
