IWK Health Centre, Halifax, Nova Scotia B3K 6R8, Canada.
Br J Ophthalmol. 2011 Apr;95(4):574-9. doi: 10.1136/bjo.2010.190116. Epub 2010 Nov 21.
The aim of this study is to assess the role of Frizzled-4 (FZD4) in familial exudative vitreoretinopathy (FEVR) and Coats disease.
Tissue samples were collected for DNA extraction and automated DNA sequencing of the two coding exons of FZD4 in both directions. Cases carrying a FZD4 mutation and demonstrating extreme disease severity were selected for direct automated sequencing of all coding exons of LRP5, NDP and TSPAN12. Clinical data were obtained for the purpose of identifying genotype-phenotype correlations.
68 probands were diagnosed as having autosomal dominant or sporadic FEVR. Eleven FZD4 mutations (five missense, three deletions, one insertion, two nonsense) were identified. Six of these mutations are novel, and none were found in 346 control chromosomes. In 16 cases of Coats disease, one polymorphism combination was found in two samples: no mutations were detected. No genotype-phenotype correlation emerged. Three severely affected cases with FZD4 mutations failed to show additional mutations in the three other FEVR genes.
The authors identified 12 FEVR probands with FZD4 mutations. FZD4 mutation screening can be a useful tool especially in mild or atypical cases of FEVR. Germ-line mutations in FZD4 do not appear to be a common cause of Coats disease.
本研究旨在评估卷曲蛋白 4（FZD4）在家族性渗出性玻璃体视网膜病变（FEVR）和 Coats 病中的作用。
采集组织样本进行 DNA 提取，并对 FZD4 的两个编码外显子进行自动 DNA 测序。选择携带 FZD4 突变且表现出极端疾病严重程度的病例，对 LRP5、NDP 和 TSPAN12 的所有编码外显子进行直接自动测序。为了确定基因型-表型相关性，收集了临床数据。
诊断为常染色体显性或散发 FEVR 的 68 名先证者。鉴定出 11 种 FZD4 突变（5 种错义突变，3 种缺失突变，1 种插入突变，2 种无义突变）。其中 6 种为新突变，在 346 条对照染色体中均未发现。在 16 例 Coats 病中，在两个样本中发现了一种多态性组合：未检测到突变。未发现基因型-表型相关性。3 例 FZD4 突变的严重受累病例未能在其他 3 个 FEVR 基因中发现额外的突变。
作者鉴定出 12 例 FZD4 突变的 FEVR 先证者。FZD4 突变筛查可能是一种有用的工具，特别是在轻度或非典型 FEVR 病例中。FZD4 的种系突变似乎不是 Coats 病的常见原因。
