Unraveling the genetic cause of a consanguineous family with unilateral coloboma and retinoschisis: expanding the phenotypic variability of RAX mutations.
Unraveling the genetic cause of a consanguineous family with unilateral coloboma and retinoschisis: expanding the phenotypic variability of RAX mutations.
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揭开与单侧造口和视网膜菌的近亲家族的遗传原因：扩大RAX突变的表型变异性。
DOI：
10.1038/s41598-017-09276-0
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发表时间：
2017-08-22
影响因子：
4.6
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Huang XF;Huang ZQ;Lin D;Dai ML;Wang QF;Chen ZJ;Jin ZB;Wang Y
眼缺损是一种常见的眼部畸形，由于人类视裂在发育过程中闭合不全而引起。多种基因突变促成了疾病过程，显示了广泛的遗传异质性和复杂性的缺损谱系疾病。在本研究中，我们的目的是解开一个近亲家庭的遗传原因，单侧缺损和视网膜劈裂。招募受试者并进行专门的眼科临床检查。全外显子组测序（WES），纯合性定位，和全面的变异分析相结合，以揭示致病突变。RAX基因中只有一个纯合突变（c.113 T > C，p.I38T）在我们严格的变异筛选过程中幸存下来，符合常染色体隐性遗传模式。该突变在家族中完全分离，并且位于高度保守的功能结构域中。晶体结构模拟表明，I38T影响蛋白质结构。我们描述了一个来自中国血缘家族的罕见眼缺损患者，该患者被证实存在一种新的RAX突变（c.113 T > C，p.I38T，纯合子），扩大了眼缺损和RAX突变的表型变异性。
Ocular coloboma is a common eye malformation arising from incomplete closure of the human optic fissure during development. Multiple genetic mutations contribute to the disease process, showing extensive genetic heterogeneity and complexity of coloboma spectrum diseases. In this study, we aimed to unravel the genetic cause of a consanguineous family with unilateral coloboma and retinoschisis. The subjects were recruited and underwent specialized ophthalmologic clinical examination. A combination of whole exome sequencing (WES), homozygosity mapping, and comprehensive variant analyses was performed to uncover the causative mutation. Only one homozygous mutation (c.113 T > C, p.I38T) in RAX gene survived our strict variant filtering process, consistent with an autosomal recessive inheritance pattern. This mutation segregated perfectly in the family and is located in a highly conserved functional domain. Crystal structure modeling indicated that I38T affected the protein structure. We describe a patient from a consanguineous Chinese family with unusual coloboma, proven to harbor a novel RAX mutation (c.113 T > C, p.I38T, homozygous), expanding the phenotypic variability of ocular coloboma and RAX mutations.
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影响因子：
3.8
作者：
Slavotinek, Anne M.
通讯作者：
Slavotinek, Anne M.
下一代测序揭示了一大群遗传性视网膜营养不良患者的基因型-表型相关性和突变谱
影响因子：
8.8
作者：
Huang, Xiu-Feng;Huang, Fang;Jin, Zi-Bing
通讯作者：
Jin, Zi-Bing
影响因子：
3.5
作者：
Lequeux, L.;Rio, M.;Calvas, P.
通讯作者：
Calvas, P.
严重综合征性视网膜纤毛病中的 POC1B 突变。
影响因子：
3.9
作者：
Beck, Bodo B.;Phillips, Jennifer B.;Bartram, Melte P.;Wegner, Jeremy;Thoenes, Michaele;Pannes, Andrea;Sampson, Josephina;Heller, Raoul;Goebel, Heike;Koerber, Friederike;Neugebauer, Antje;Hedergott, Andrea;Nuernberg, Gudrun;Nuernberg, Peter;Thiele, Holger;Altmueller, Janine;Toliat, Mohammad R.;Staubach, Simon;Boycott, Kym M.;Valente, Enza Maria;Janecke, Andreas R.;Eisenberger, Tobias;Bergmann, Carsten;Tebbe, Lars;Wang, Yang;Wu, Yundong;Fry, Andrew M.;Westerfield, Monte;Wolfrum, Uwe;Bolz, Hanno J.
通讯作者：
Bolz, Hanno J.
影响因子：
2.7
作者：
Pan, Yi;Martinez-De Luna, Reyna I.;El-Hodiri, Heithem M.
通讯作者：
El-Hodiri, Heithem M.