Identification of a novel ZNF469 mutation in a large family with Ehlers-Danlos phenotype
Identification of a novel ZNF469 mutation in a large family with Ehlers-Danlos phenotype
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DOI：
10.1016/j.gene.2012.09.022
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发表时间：
2012-12-15
期刊：
影响因子：
3.5
通讯作者：
Alkuraya, Fowzan S.
中科院分区：
文献类型：
--
作者：
Al-Owain, Mohammed;Al-Dosari, Mohammed S.;Alkuraya, Fowzan S.
脆性角膜综合征(BCS)是一种遗传性异质性疾病，其特征是高度的角膜脆性和变薄，可导致自发性或外伤性角膜破裂。BCS-1和BCS-2分别由ZNF469和Prdm5的隐性突变引起。这两个基因都在角膜发育和维护的调节途径中发挥作用。我们报告一个血缘关系密切的家庭，有5名患者患有BCS的主要眼部特征，并有显著的肌肉骨骼表现，主要表现为关节过度活动和严重的脊柱后凸。患者皮肤较薄，拇指外翻，变异性感音神经性耳聋和蛛网膜炎。有趣的是，其中一名患者还患有苯丙酮尿症，并表现出比他的兄弟姐妹更温和的眼科和肌肉骨骼表型。尿吡啶酚和脱氧吡啶酚浓度及其比值轻度升高，提示骨胶原代谢增加。直接测序发现ZNF469基因外显子2(C.8817_8830dup)存在一个新的14个碱基的纯合重复序列。这个家系突出了BCS和Ehler-Danlos综合征之间的表型重叠。(C)2012爱思唯尔B.V.保留所有权利。
Brittle cornea syndrome (BCS) is a genetically heterogeneous disorder characterized by extreme corneal fragility and thinning, which may lead to spontaneous or trauma-induced corneal rupture. BCS-1 and BCS-2 are caused by recessive mutations in ZNF469 and PRDM5, respectively. Both genes play a role in the regulatory pathway of corneal development and maintenance. We report a consanguineous family with five patients affected with the cardinal ocular features of BCS and significant musculoskeletal findings primarily in the form of joint hypermobility and severe kyphoscoliosis. The patients had thin velvety skin, hallux valgus, variable sensorineural hearing loss and arachnodactyly. Interestingly, one of the patients additionally had phenylketonuria and showed a milder ophthalmological and musculoskeletal phenotype than his affected siblings. The urinary pyridinoline and deoxypyridinoline concentrations and their ratios were mildly elevated indicating increased bone-collagen turnover. A novel homozygous 14 bp duplication in exon 2 of ZNF469 (c.8817_8830dup) was uncovered by direct sequencing. This family highlights the phenotypic overlap between BCS and Ehlers-Danlos syndrome. (C) 2012 Elsevier B.V. All rights reserved.