特殊表型遗传性先天性白内障的超微结构和基因定位

目的 探讨一表型特殊、晶状体呈簇状混浊的常染色体显性遗传性先天性白内障(ADCC)的超微结构,并初步定位该疾病的相关候选基因。方法 收集特殊表型ADCC一家系资料,对家系成员行眼部检查;在光学显微镜和透射电镜下观察晶状体细胞超微结构的改变;选择γ-晶状体蛋白基因附近多个微卫星位点,对该家系ADCC疾病相关候选基因进行连锁分析。结果 光学显微镜下特殊表型ADCC患者晶状体纤维细胞失去正常排列规则,产生不规则折光,并可见网格样改变、黏液样变性及结晶样物质析出等局灶性退行性变;透射电镜下可见细胞皱缩、变形,失去正常长六边形形态,细胞间隙增宽,细胞内可见异常高密度球形颗粒沉着。连锁分析结果显示,该家系ADCC疾病相关候选基因与微卫星位点D2S2208、D2S2382及D2S164连锁,最大LOD值为3．34。结论 特殊表型ADCC的特异性病理学改变集中在晶状体纤维细胞,其疾病相关候选基因极可能为γ-晶状体蛋白基因。（中华眼科杂志,2004,40：306-310)

Study on ultrastructure changes and the genetic locus for a special phenotype cataract

OBJECTIVE: To report the ultrastructure changes and map the genetic locus for a special phenotype autosomal dominant congenital cataract (ADCC) in a large Chinese family. METHODS: A large four-generation Chinese family affected by this special phenotype ADCC was analyzed. Clinical examinations, light and transmission electron microscopy analysis of the removed lens tissue were performed. Blood samples were taken for DNA extraction and two-point linkage analyses between the polymorphisms of microsatellite markers near the gamma-crystallin gene (CRYG) and the disease-associated locus was also determined. RESULTS: The lens fiber cells displayed abnormal inter- and intracellular alterations, including irregular refractivity, focal degeneration and irregular and enlarged intracellular spaces. Linkage analysis showed that there was linkage between the ADCC disease-associated locus and D2S2208, D2S2382 and D2S164. CONCLUSIONS: There were characteristic alterations to the lens fiber cells of this special phenotype ADCC and the CRYGD gene might be the disease-associated.