Two heterozygous mutations identified in one Chinese patient with bilateral macular coloboma

Li,Tao; Lin,Ying; Gao,Hongbin; Chen,Chuan; Zhu,Yi; Liu,Bingqian; Lian,Yu; Li,Yonghao; Zhou,Wenli; Jiang,Hongye; Li,Haichun; Wu,Qingxiu; Liang,Xiaoling; Jin,Chenjin; Huang,Xinhua; Lu,Lin

doi:10.3892/mmr.2017.6887

Two heterozygous mutations identified in one Chinese patient with bilateral macular coloboma

Authors:
- Tao Li
- Ying Lin
- Hongbin Gao
- Chuan Chen
- Yi Zhu
- Bingqian Liu
- Yu Lian
- Yonghao Li
- Wenli Zhou
- Hongye Jiang
- Haichun Li
- Qingxiu Wu
- Xiaoling Liang
- Chenjin Jin
- Xinhua Huang
- Lin Lu
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Affiliations: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China, Department of Toxicology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510000, P.R. China
Published online on: June 29, 2017 https://doi.org/10.3892/mmr.2017.6887
Pages: 2505-2510
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Congenital macular coloboma is characterized by defined punched out atrophic lesions of the macula. The present study aimed to investigate the genetic alterations of one Chinese sporadic patient with bilateral large macular coloboma. Complete ophthalmic examinations, including best‑corrected visual acuity, slit‑lamp examination, fundus examination, fundus photograph and fundus fluorescein angiography imaging, Pentacam, and optical coherence tomography were performed on the patient. Genomic DNA was extracted from leukocytes in a peripheral blood sample collected from the patient, the patient's unaffected family members and from 200 unrelated control subjects from the same population. Next‑generation sequencing of the known genes involved in ocular disease was performed. The functional effects of the mutation were analyzed using Polymorphism Phenotyping (PolyPhen) and Sorting Intolerant From Tolerant (SIFT). One heterozygous bestrophin 1 (BEST1) mutation c.1037C>A (p.Pro346His, p.P346H) in exon 9 and one heterozygous regulating synaptic membrane exocytosis 1 (RIMS1) mutation c.3481A>G (p.Arg1161Gly, p.R1161G) in exon 23 were identified in the patient being investigated, but not in the unaffected family members or unrelated control subjects. Polyphen and SIFT predicted that the amino acid substitution p.P346H in the BEST1 protein is damaging. In addition, Polyphen predicted that the amino acid substitution p.R1161G in the RIM1 protein is damaging. The results of the current study have increased the mutation spectrums of BEST1 and RIMS1, and are valuable for improving the current genetic counseling process and developing novel therapeutic interventions for patients with macular coloboma.

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