Toomes Carmel, Bottomley Helen M, Jackson Richard M, Towns Katherine V, Scott Sheila, Mackey David A, Craig Jamie E, Jiang Li, Yang Zhenglin, Trembath Richard, Woodruff Geoffrey, Gregory-Evans Cheryl Y, Gregory-Evans Kevin, Parker Michael J, Black Graeme C M, Downey Louise M, Zhang Kang, Inglehearn Chris F
Molecular Medicine Unit, University of Leeds, Leeds, United Kingdom.
Am J Hum Genet. 2004 Apr;74(4):721-30. doi: 10.1086/383202. Epub 2004 Mar 11.
Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder of the retinal vascular system. Autosomal dominant FEVR is genetically heterogeneous, but its principal locus, EVR1, is on chromosome 11q13-q23. The gene encoding the Wnt receptor frizzled-4 (FZD4) was recently reported to be the EVR1 gene, but our mutation screen revealed fewer patients harboring mutations than expected. Here, we describe mutations in a second gene at the EVR1 locus, low-density-lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor. This finding further underlines the significance of Wnt signaling in the vascularization of the eye and highlights the potential dangers of using multiple families to refine genetic intervals in gene-identification studies.
家族性渗出性玻璃体视网膜病变（FEVR）是一种视网膜血管系统的遗传性致盲疾病。常染色体显性遗传的FEVR在遗传上具有异质性，但其主要位点EVR1位于11号染色体的11q13 - q23区域。最近有报道称，编码Wnt受体卷曲蛋白4（FZD4）的基因就是EVR1基因，但我们的突变筛查发现携带突变的患者比预期的要少。在此，我们描述了EVR1位点的第二个基因——低密度脂蛋白受体相关蛋白5（LRP5，一种Wnt共受体）中的突变。这一发现进一步强调了Wnt信号在眼部血管形成中的重要性，并突出了在基因识别研究中使用多个家系来细化遗传区间时的潜在风险。
