Brooks David G, Manova-Todorova Katia, Farmer Jennifer, Lobmayr Lioba, Wilson Robert B, Eagle Ralph C, St Pierre Tim G, Stambolian Dwight
Division of Medical Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Invest Ophthalmol Vis Sci. 2002 Apr;43(4):1121-6.
Hereditary hyperferritinemia cataract syndrome (HHCS) is a genetic disease defined by cataracts, hyperferritinemia, and ferritin light-chain (L-ferritin) gene mutations. HHCS was diagnosed in this study in one of the first families known to be affected in the United States, and the basis of lens opacities in HHCS was determined.
DNA amplification and sequencing of the human L-ferritin gene was used for mutation detection. RNA electrophoretic mobility shift analysis was performed to demonstrate functional consequences of a new mutation. Opacities were characterized by immunohistochemical and electron microscopic analyses of human HHCS lens aspirate.
HHCS was diagnosed in five members of one family who had all three hallmark features: hyperferritinemia, a prominent cataract or history, and the finding of a novel mutation in the L-ferritin gene (C33T). This mutation interferes with function of the L-ferritin transcript in an RNA gel shift assay. Light-diffracting crystalline deposits were present in cataractous lenses from two affected family members but not in control lenses. Immunohistochemical analysis showed strong anti-L-ferritin reactivity in the crystalline deposits. Analysis of these deposits by transmission electron microscopy with fast Fourier transformation demonstrated macromolecular crystalline structure of the deposits. The data were consistent with a face-centered cubic crystal having a unit crystal cell size of 17 nm, both findings characteristic of ferritin crystals grown in vitro.
HHCS cataract is due to numerous small opacities, predominantly in the lens cortex, that are light-diffracting ferritin crystals. Patients with HHCS may be recognized by a family history of cataracts and hyperferritinemia without increased serum iron.
遗传性高铁蛋白血症白内障综合征（HHCS）是一种由白内障、高铁蛋白血症和铁蛋白轻链（L-铁蛋白）基因突变所定义的遗传性疾病。本研究在美国首批已知受影响的家族之一中诊断出HHCS，并确定了HHCS晶状体混浊的病因。
采用人L-铁蛋白基因的DNA扩增和测序进行突变检测。进行RNA电泳迁移率变动分析以证明新突变的功能后果。通过对人HHCS晶状体吸出物进行免疫组织化学和电子显微镜分析来表征混浊情况。
在一个家族的五名成员中诊断出HHCS，他们都具有三个标志性特征：高铁蛋白血症、明显的白内障或病史，以及在L-铁蛋白基因中发现新突变（C33T）。在RNA凝胶迁移试验中，该突变干扰了L-铁蛋白转录物的功能。两名受影响家族成员的白内障晶状体中存在光衍射晶体沉积物，而对照晶状体中没有。免疫组织化学分析显示晶体沉积物中有强烈的抗L-铁蛋白反应性。通过透射电子显微镜结合快速傅里叶变换对这些沉积物进行分析，证实了沉积物的大分子晶体结构。数据与面心立方晶体一致，其单位晶胞大小为17nm，这两个发现都是体外生长的铁蛋白晶体的特征。
HHCS白内障是由于大量小混浊，主要位于晶状体皮质，这些混浊是光衍射铁蛋白晶体。HHCS患者可能通过白内障和高铁蛋白血症家族史被识别，且血清铁不升高。
