A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency
A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency
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DOI：
10.1007/s00439-010-0820-9
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发表时间：
2010-06-01
期刊：
影响因子：
5.3
通讯作者：
Gat-Yablonski, Galia
中科院分区：
文献类型：
--
作者：
Ashkenazi-Hoffnung, Liat;Lebenthal, Yael;Gat-Yablonski, Galia
编码转录因子OTX2基因的杂合突变最近被证明是眼部和垂体异常的原因。在这里，我们描述了一个单侧无眼和身材矮小的病人。下丘脑-垂体轴内分泌评价显示孤立性生长激素缺乏症（IGHD）伴垂体前叶小、柄不可见、后叶异位、右侧无眼。分析HESX1、SOX2和OTX2基因的DNA突变。分子分析在同源域内发现了一个新的杂合OTX2突变（c.270A >t, p.R90S）。功能分析表明，该突变抑制了该蛋白的DNA结合和反活化活性。这种新的功能丧失突变与西班牙系犹太血统患者的眼失和IGHD有关。我们建议GH缺乏和眼部畸形的患者，如果对经典转录因子基因（PROP1, POU1F1， HESX1和LHX4）的遗传分析未能发现改变，则应检查OTX2基因是否存在突变。
Heterozygous mutations of the gene encoding transcription factor OTX2 were recently shown to be responsible for ocular as well as pituitary abnormalities. Here, we describe a patient with unilateral anophthalmia and short stature. Endocrine evaluation of the hypothalamic-pituitary axis revealed isolated growth hormone deficiency (IGHD) with small anterior pituitary gland, invisible stalk, ectopic posterior lobe, and right anophthalmia on brain magnetic resonance imaging. DNA was analyzed for mutations in the HESX1, SOX2, and OTX2 genes. Molecular analysis yielded a novel heterozygous OTX2 mutation (c.270A > T, p.R90S) within the homeodomain. Functional analysis revealed that the mutation inhibited both the DNA binding and transactivation activities of the protein. This novel loss-of-function mutation is associated with anophthalmia and IGHD in a patient of Sephardic Jewish descent. We recommend that patients with GH deficiency and ocular malformation in whom genetic analysis for classic transcription factor genes (PROP1, POU1F1, HESX1, and LHX4) failed to identify alterations should be checked for the presence of mutations in the OTX2 gene.