Whole exome sequencing identified novel CRB1 mutations in Chinese and Indian populations with autosomal recessive retinitis pigmentosa

Yin Yang; Yeming Yang; Lulin Huang; Yaru Zhai; Jie Li; Zhilin Jiang; Bo Gong; Hao Fang; Ramasamy Kim; Zhenglin Yang; Periasamy Sundaresan; Xianjun Zhu; Yu Zhou

doi:10.1038/srep33681

Whole exome sequencing identified novel CRB1 mutations in Chinese and Indian populations with autosomal recessive retinitis pigmentosa

Sci Rep. 2016 Sep 27:6:33681. doi: 10.1038/srep33681.

Authors

Yin Yang^{1

2}, Yeming Yang^{1

3

4

5}, Lulin Huang^{1

3}, Yaru Zhai¹, Jie Li², Zhilin Jiang^{1

3}, Bo Gong^{1

3}, Hao Fang^{1

3}, Ramasamy Kim⁶, Zhenglin Yang^{1

3

5}, Periasamy Sundaresan⁷, Xianjun Zhu^{1

3

4

5

8}, Yu Zhou^{1

3

5

8}

Affiliations

¹ Sichuan Provincial Key Laboratory for Human Disease Gene Study, School of Medicine, Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
² Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
³ Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
⁴ Institute of Laboratory Animal Sciences, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
⁵ Key Laboratory for NeuroInformation of Ministry of Education and Medicine Information Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
⁶ Retina-vitreous services, Aravind Eye Hospital, Madurai, Tamilnadu, India.
⁷ Department of Genetics, Aravind Medical Research Foundation, Aravind Eye Hospital, Madurai, Tamilnadu, India.
⁸ Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, Sichuan, China.

Abstract

Retinitis pigmentosa (RP) is a leading cause of inherited blindness characterized by progressive degeneration of the retinal photoreceptor cells. This study aims to identify genetic mutations in a Chinese family RP-2236, an Indian family RP-IC-90 and 100 sporadic Indian individuals with autosomal recessive RP (arRP). Whole exome sequencing was performed on the index patients of RP-2236, RP-IC-90 and all of the 100 sporadic Indian patients. Direct Sanger sequencing was used to validate the mutations identified. Four novel mutations and one reported mutation in the crumbs homolog 1 (CRB1) gene, which has been known to cause severe retinal dystrophies, were identified. A novel homozygous splicing mutation c.2129-1G>C was found in the three patients In family RP-2236. A homozygous point mutation p.R664C was found in RP-IC-90. A novel homozygous mutation p.G1310C was identified in patient I-44, while novel compound heterozygous mutations p.N629D and p.A593T were found in patient I-7. All mutations described above were not present in the 1000 normal controls. In conclusion, we identified four novel mutations in CRB1 in a cohort of RP patients from the Chinese and Indian populations. Our data enlarges the CRB1 mutation spectrums and may provide new target loci for RP diagnose and treatment.