Genetic variations in Bestrophin‑1 and associated clinical findings in two Chinese patients with juvenile‑onset and adult‑onset best vitelliform macular dystrophy

Lin,Ying; Li,Tao; Ma,Chenghong; Gao,Hongbin; Chen,Chuan; Zhu,Yi; Liu,Bingqian; Lian,Yu; Huang,Ying; Li,Haichun; Wu,Qingxiu; Liang,Xiaoling; Jin,Chenjin; Huang,Xinhua; Ye,Jianhua; Lu,Lin

doi:10.3892/mmr.2017.7927

Genetic variations in Bestrophin‑1 and associated clinical findings in two Chinese patients with juvenile‑onset and adult‑onset best vitelliform macular dystrophy

Authors:
- Ying Lin
- Tao Li
- Chenghong Ma
- Hongbin Gao
- Chuan Chen
- Yi Zhu
- Bingqian Liu
- Yu Lian
- Ying Huang
- Haichun Li
- Qingxiu Wu
- Xiaoling Liang
- Chenjin Jin
- Xinhua Huang
- Jianhua Ye
- 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 Endocrine, College of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China, Guangdong Laboratory Animals Monitoring Institute, Key Laboratory of Guangdong Laboratory Animals, Guangzhou, Guangdong 510640, P.R. China
Published online on: October 27, 2017 https://doi.org/10.3892/mmr.2017.7927
Pages: 225-233
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Best vitelliform macular dystrophy (BVMD) is a hereditary retinal disease characterized by the bilateral accumulation of large egg yolk‑like lesions in the sub‑retinal and sub‑retinal pigment epithelium spaces. Macular degeneration in BVMD can begin in childhood or adulthood. The variation in the age of onset is not clearly understood. The present study characterized the clinical characteristics of two Chinese patients with either juvenile‑onset BVMD or adult‑onset BVMD and investigated the underlying genetic variations. A 16‑year‑old male (Patient 1) was diagnosed with juvenile‑onset BVMD and a 43‑year‑old female (Patient 2) was diagnosed with adult‑onset BVMD. Comprehensive ophthalmic examinations were performed, including best‑corrected visual acuity, intraocular pressure, slit‑lamp examination, fundus photography, optical coherence tomography, fundus fluorescein angiography imaging and Espion electrophysiology. Genomic DNA was extracted from peripheral blood leukocytes collected from these patients, their family members, and 200 unrelated subjects within in the same population. The 11 exons of the bestrophin‑1 (BEST1) gene were amplified by polymerase chain reaction and directly sequenced. Both patients presented lesions in the macular area. In Patient 1, a heterozygous mutation c.903T>G (p.D301E) in exon 8 of the BEST1 gene was identified. This mutation was not present in any of the unaffected family members or the normal controls. Polymorphism phenotyping and the sorting intolerant from tolerant algorithm predicted that the amino acid substitution D301E in bestrophin‑1 protein was damaging. In Patient 2, a single nucleotide polymorphism c.1608C>T (p.T536T) in exon 10 of the BEST1 gene was identified. These findings expand the spectrum of BEST1 genetic variation and will be valuable for genetic counseling and the development of therapeutic interventions for patients with BVMD.

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