van de Ven Johannes P H, Boon Camiel J F, Fauser Sacha, Hoefsloot Lies H, Smailhodzic Dzenita, Schoenmaker-Koller Frederieke, Klevering Jeroen, Klaver Caroline C W, den Hollander Anneke I, Hoyng Carel B
Department of Ophthalmology, Radboud University Medical Center, Philips van Leydenlaan, 6525 EX Nijmegen, the Netherlands.
Arch Ophthalmol. 2012 Aug;130(8):1038-47. doi: 10.1001/archophthalmol.2012.265.
To identify novel complement factor H (CFH) gene mutations and to specify the clinical characteristics in patients with basal laminar drusen (BLD), a clinical subtype of age-related macular degeneration.
Twenty-one probands with BLD were included in this study. The ophthalmic examination included nonstereoscopic 30° color fundus photography, fluorescein angiography, and high-resolution spectral-domain optical coherence tomography. Renal function was tested by measurement of serum creatinine and urea nitrogen levels. Venous blood samples were drawn for genomic DNA, and all coding exons and splice junctions of the CFH gene were analyzed by direct sequencing.
In 3 families, we identified novel heterozygous mutations in theCFHgene: p.Ile184fsX, p.Lys204fsX, and c.1697-17_-8del. Ten of 13 mutation carriers displayed the BLD phenotype with a wide variety in clinical presentation, ranging from limited macular drusen to extensive drusen in the posterior pole as well as the peripheral retina. Two patients with BLD developed endstage kidney disease as a result of membranoproliferative glomerulonephritis type II.
The early-onset BLD phenotype can be caused by heterozygous mutations in the CFH gene. Because some patients with BLD are at risk to develop membranoproliferative glomerulonephritis type II, we recommend that patients with extensive BLD undergo screening for renal dysfunction.
Elucidation of the clinical BLD phenotype will facilitate identification of individuals predisposed to developing disease-related comorbidity, such as membranoproliferative glomerulonephritis type II. Moreover, with upcoming treatment modalities targeting specific components of the complement system, early identification of patients with BLD and detection of the genetic defect become increasingly important.
鉴定新的补体因子H（CFH）基因突变，并明确基底膜性玻璃疣（BLD）患者的临床特征，BLD是年龄相关性黄斑变性的一种临床亚型。
本研究纳入了21例BLD先证者。眼科检查包括非立体30°彩色眼底照相、荧光素血管造影和高分辨率光谱域光学相干断层扫描。通过测量血清肌酐和尿素氮水平来检测肾功能。采集静脉血样本用于提取基因组DNA，并通过直接测序分析CFH基因的所有编码外显子和剪接位点。
在3个家系中，我们在CFH基因中鉴定出了新的杂合突变：p.Ile184fsX、p.Lys204fsX和c.1697 - 17_-8del。13名突变携带者中有10名表现出BLD表型，临床表现多种多样，从局限性黄斑玻璃疣到后极部以及周边视网膜的广泛玻璃疣。2例BLD患者因II型膜增生性肾小球肾炎发展为终末期肾病。
早发型BLD表型可能由CFH基因的杂合突变引起。由于一些BLD患者有发展为II型膜增生性肾小球肾炎的风险，我们建议广泛型BLD患者进行肾功能筛查。
阐明临床BLD表型将有助于识别易发生疾病相关合并症（如II型膜增生性肾小球肾炎）的个体。此外，随着针对补体系统特定成分的新治疗方式的出现，早期识别BLD患者并检测遗传缺陷变得越来越重要。
