A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes

Abstract Congenital cavitary optic disc anomalies (CODA) is clinically typified by an enlarged excavation of optic disc in diverse degrees. Here, we report the clinical and genetic findings in a four-generation Chinese family with a complicated form of autosomal dominant CODA. Cardinal manifestation...

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Autores principales:	Decai Wang, Xinyuan Pan, Jiangdong Ji, Shun Gu, Xiantao Sun, Chao Jiang, Weiyi Xia, Zhihua Qiu, Xiaoli Kang, Sijia Ding, Qinghuai Liu, Xue Chen, Fang Lu, Chen Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/534a0124c6b9411088848a7b7ddce152
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spelling	oai:doaj.org-article:534a0124c6b9411088848a7b7ddce1522021-12-02T15:04:55ZA large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes10.1038/s41598-017-07730-72045-2322https://doaj.org/article/534a0124c6b9411088848a7b7ddce1522017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07730-7https://doaj.org/toc/2045-2322Abstract Congenital cavitary optic disc anomalies (CODA) is clinically typified by an enlarged excavation of optic disc in diverse degrees. Here, we report the clinical and genetic findings in a four-generation Chinese family with a complicated form of autosomal dominant CODA. Cardinal manifestations included bilateral excavated optic disc with multiple cilioretinal vessels emerging and bilateral retinoschisis with great variability in the range of extension and severity. Other intra-familial phenotypic diversities were also noted, including severity in retinal atrophy, onset age of visual impairment and presence of congenital nystagmus and strabismus. Genome-wide linkage analysis and fine mapping mapped a novel locus for CODA to a 34.3 cM interval between D14S972 and D14S139 at 14q12-q22.1. A maximum multi-point log odds score of 3.901 was reached at D14S275. However, no mutation was identified by exome sequencing or direct sequencing of PAX6 and PAX2 genes, suggesting that the mutation may reside within a regulatory element. In conclusion, we find retinoschisis as a necessary consequence of optic nerve head (ONH) anomalies. The complicated phenotype observed in the family provided additional insights into the inherited ONH anomalies. Mapping of a novel locus, 14q12-q22.1, implies a new disease-causing gene and potential distinct pathogenesis for CODA.Decai WangXinyuan PanJiangdong JiShun GuXiantao SunChao JiangWeiyi XiaZhihua QiuXiaoli KangSijia DingQinghuai LiuXue ChenFang LuChen ZhaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Decai Wang Xinyuan Pan Jiangdong Ji Shun Gu Xiantao Sun Chao Jiang Weiyi Xia Zhihua Qiu Xiaoli Kang Sijia Ding Qinghuai Liu Xue Chen Fang Lu Chen Zhao A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes
description	Abstract Congenital cavitary optic disc anomalies (CODA) is clinically typified by an enlarged excavation of optic disc in diverse degrees. Here, we report the clinical and genetic findings in a four-generation Chinese family with a complicated form of autosomal dominant CODA. Cardinal manifestations included bilateral excavated optic disc with multiple cilioretinal vessels emerging and bilateral retinoschisis with great variability in the range of extension and severity. Other intra-familial phenotypic diversities were also noted, including severity in retinal atrophy, onset age of visual impairment and presence of congenital nystagmus and strabismus. Genome-wide linkage analysis and fine mapping mapped a novel locus for CODA to a 34.3 cM interval between D14S972 and D14S139 at 14q12-q22.1. A maximum multi-point log odds score of 3.901 was reached at D14S275. However, no mutation was identified by exome sequencing or direct sequencing of PAX6 and PAX2 genes, suggesting that the mutation may reside within a regulatory element. In conclusion, we find retinoschisis as a necessary consequence of optic nerve head (ONH) anomalies. The complicated phenotype observed in the family provided additional insights into the inherited ONH anomalies. Mapping of a novel locus, 14q12-q22.1, implies a new disease-causing gene and potential distinct pathogenesis for CODA.
format	article
author	Decai Wang Xinyuan Pan Jiangdong Ji Shun Gu Xiantao Sun Chao Jiang Weiyi Xia Zhihua Qiu Xiaoli Kang Sijia Ding Qinghuai Liu Xue Chen Fang Lu Chen Zhao
author_facet	Decai Wang Xinyuan Pan Jiangdong Ji Shun Gu Xiantao Sun Chao Jiang Weiyi Xia Zhihua Qiu Xiaoli Kang Sijia Ding Qinghuai Liu Xue Chen Fang Lu Chen Zhao
author_sort	Decai Wang
title	A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes
title_short	A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes
title_full	A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes
title_fullStr	A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes
title_full_unstemmed	A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes
title_sort	large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/534a0124c6b9411088848a7b7ddce152
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A large family with inherited optic disc anomalies: a correlation between a new genetic locus and complex ocular phenotypes

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