Clinical and next-generation sequencing findings in a Chinese family exhibiting severe familial exudative vitreoretinopathy

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

doi:10.3892/ijmm.2017.3308

Clinical and next-generation sequencing findings in a Chinese family exhibiting severe familial exudative vitreoretinopathy

Authors:
- Ying Lin
- Hongbin Gao
- Chuan Chen
- Yi Zhu
- Tao Li
- Bingqian Liu
- Chenghong Ma
- Hongye Jiang
- Yonghao Li
- Ying Huang
- Qingxiu Wu
- Haichun Li
- Xiaoling Liang
- Chenjin Jin
- Jianhua Ye
- 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 Endocrine, College of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, 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: December 5, 2017 https://doi.org/10.3892/ijmm.2017.3308
Pages: 773-782
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Familial exudative vitreoretinopathy (FEVR) is a rare hereditary retinal disorder characterized by the premature arrest of vascularization in the peripheral retina. The aim of the present study was to characterize the clinical presentations of a Chinese family affected by bilateral severe FEVR, and to identify the underlying genetic variations. One family that presented with bilateral FEVR was recruited for this study. Comprehensive ophthalmic examinations, including best‑corrected visual acuity, slit‑lamp examination, fundus photography, fundus fluorescein angiography imaging and electroretinogram were performed. Genomic DNA was extracted from leukocytes of the peripheral blood collected from the affected and unaffected family members, as well as 200 unrelated control subjects from the same population. Next‑generation sequencing of the candidate genes associated with ocular diseases was performed, and the identified mutations were validated by conventional polymerase chain reaction‑based sequencing. The functional effects of the mutations were analyzed by polymorphism phenotyping (PolyPhen) and sorting intolerant from tolerant (SIFT). One heterozygous ATP binding cassette subfamily A member 4 (ABCA4) c.5693G>A (p.R1898H) mutation in exon 40 and one heterozygous LDL receptor related protein 5 (LRP5) c.260T>G (p.I87S) mutation in exon 2 were identified in this family. To the best of our knowledge, the ABCA4 c.5693G>A (p.R1898H) mutation has not been reported in FEVR, and the LRP5 c.260T>G (p.I87S) mutation is a novel mutation. PolyPhen and SIFT predicted that the amino acid substitution R1898H in protein ABCA4 is benign, whereas the amino acid substitution I87S in protein LRP5 is damaging. A single nucleotide polymorphism c.266A>G (p.Q89R, rs41494349) was identified in exon 2 of LRP5. These findings expand the mutation spectrums of ABCA4 and LRP5, and will be valuable for genetic counseling and development of therapeutic interventions for patients with FEVR.

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