Concurrent deletion of BMP4 and OTX2 genes, two master genes in ophthalmogenesis
Concurrent deletion of BMP4 and OTX2 genes, two master genes in ophthalmogenesis
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DOI：
10.1016/j.ejmg.2012.10.007
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发表时间：
2013-01-01
影响因子：
1.9
通讯作者：
Kosaki, Kenjiro
中科院分区：
文献类型：
--
作者：
Takenouchi, Toshiki;Nishina, Sachiko;Kosaki, Kenjiro
BMP4和OTX2是眼形成的主控基因。BMP4和OTX2突变常导致眼缺陷，包括眼无-小眼。据报道，BMP4或OTX2突变的杂合个体具有显著程度的可变表达性。有趣的是，BMP4和OTX2都驻留在14q22上，相距只有2.8 Mb。先前的研究报道，在3例涉及BMP4和OTX2的14q22缺失患者中，所有患者都有严重的眼部缺陷。BMP4和OTX2基因双缺失个体的可变表达度最低，这可能归因于在动物模型中观察到的这两个基因的组合关系。我们在此报告一位BMP4和OTX2同时缺失的患者，他表现出双侧小眼症，更具体地说，是前节发育不良伴小角膜。进化上保守的Bmp4和Otx2位点的物理连锁可能表明这两个基因的近端排列具有优势。另一个显著特征是连续神经成像观察到的渐进性白质丢失。对12例先前报道的14q22微缺失患者的回顾显示，一半患者的白质体积减少。白质病变是否具有年龄依赖性和进行性，仍有待阐明。总之，眼前节缺损，特别是在神经影像学上伴有白质体积减少时，应引起临床对14q22微缺失的怀疑。(c) 2012年Elsevier Masson SAS。版权所有。
BMP4 and OTX2 are master genes in ophthalmogenesis. Mutations of BMP4 and OTX2 often lead to eye defects, including anophthalmia-microphthalmia. A significant degree of variable expressivity has been reported in heterozygous individuals with BMP4 or OTX2 mutation. Interestingly, both BMP4 and OTX2 reside on 14q22, being only 2.8 Mb apart. Previous studies reported that among three patients with 14q22 deletion involving BMP4 and OTX2, all had severe eye defects. The minimal degree of variable expressivity among these individuals who were doubly deleted for BMP4 and OTX2 could be attributed to the combinatorial relationship of the two genes observed in animal models. We herein report a patient with a concurrent deletion of BMP4 and OTX2 who exhibited bilateral microphthalmia, more specifically, anterior segment dysgenesis with microcornea. Evolutionarily conserved physical linkage of Bmp4 and Otx2 loci may suggest an advantage of the proximal alignment of the two genes. Another striking feature in the propositus was the progressive white matter loss observed by serial neuroimaging. A review of twelve previously reported patients with 14q22 microdeletion revealed decreased white matter volume in half of the patients. It remains to be elucidated whether the white matter lesion is age-dependent and progressive. In conclusion, anterior segment defects of the eyes, especially when accompanied by decreased white matter volume on neuroimaging, should raise the clinical suspicion of 14q22 microdeletion. (c) 2012 Elsevier Masson SAS. All rights reserved.