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Sci Rep. 2017 Aug 10;7(1):7799. doi: 10.1038/s41598-017-07730-7.

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

Wang D1, Pan X2, Ji J3, Gu S4, Sun X5, Jiang C3, Xia W3, Qiu Z6, Kang X7, Ding S3, Liu Q3, Chen X8,9,10, Lu F11, Zhao C12,13,14.

Author information

1
Department of Preventive Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
2
Department of Ophthalmology, The Affliated Wuhu No. 2 People's Hospital of Wannan Medical College, Wuhu, 241000, China.
3
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 210029, China.
4
Department of Ophthalmology, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, 214023, China.
5
Department of Ophthalmology, Children Hospital of Zhengzhou, Zhengzhou, 450053, China.
6
Department of Ophthalmology, Dongyuan Hospital of traditional Chinese medicine, Heyuan, 517000, China.
7
Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
8
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 210029, China. drcx1990@163.com.
9
Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China. drcx1990@163.com.
10
Key Laboratory of Myopia of State Health Ministry (Fudan University) and Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China. drcx1990@163.com.
11
Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, China. lufang@medmail.com.cn.
12
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, 210029, China. dr_zhaochen@163.com.
13
Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China. dr_zhaochen@163.com.
14
Key Laboratory of Myopia of State Health Ministry (Fudan University) and Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China. dr_zhaochen@163.com.

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.

PMID:
28798362
PMCID:
PMC5552876
DOI:
10.1038/s41598-017-07730-7
[Indexed for MEDLINE]
Free PMC Article

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