Identification of CRB1 mutations in two Chinese consanguineous families exhibiting autosomal recessive retinitis pigmentosa

Guo,Xiaoxin; Li,Jie; Wang,Qingwei; Shu,Yi; Wang,Jin; Chen,Lijia; Zhang,Houbin; Shi,Yi; Yang,Jiyun; Lu,Fang; Jiang,Li; Qu,Chao; Gong,Bo

doi:10.3892/mmr.2019.10495

Identification of CRB1 mutations in two Chinese consanguineous families exhibiting autosomal recessive retinitis pigmentosa

Authors:
- Xiaoxin Guo
- Jie Li
- Qingwei Wang
- Yi Shu
- Jin Wang
- Lijia Chen
- Houbin Zhang
- Yi Shi
- Jiyun Yang
- Fang Lu
- Li Jiang
- Chao Qu
- Bo Gong
View Affiliations

Affiliations: Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, P.R. China, Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, P.R. China, Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, P.R. China
Published online on: July 12, 2019 https://doi.org/10.3892/mmr.2019.10495
Pages: 2922-2928

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Retinitis pigmentosa (RP) is a leading cause of inherited blindness characterized by progressive loss of retinal photoreceptor cells. The present study aimed to identify the causative gene mutations in two Chinese families with autosomal recessive retinitis pigmentosa (arRP). Two Chinese consanguineous arRP families (RP‑2284 and RP‑2360) were recruited in this study, involving totally three affected and 25 unaffected members. All the affected members underwent a complete ophthalmic examination, including fundus photography, multifocal electroretinography (ERG) and full field ERG. Exome sequencing was performed on the three RP patients in the two families, followed by direct Sanger sequencing in all the family members and in 1,260 unrelated controls for validation of the mutations identified. Two homozygous missense mutations in the crumbs homolog 1 (CRB1) gene, which is known to cause severe retinal dystrophies, were found to be related to the phenotype of the two arRP families. The homozygous missense mutation c.1997 T>A in CRB1 was detected in two patients in the RP‑2284 family. The proband in the RP‑2360 family was the only RP patient and was found to carry the novel homozygous missense mutation c.2426 A>C in CRB1. The two mutations were heterozygous or absent in the other healthy family members, and they were absent in the 1,260 controls. The amino acid changes in the CRB1 protein affected by the two mutations were predicted to be damaging by Polyohen‑2. Our study reported two CRB1 mutations causing arRP in two Chinese families, which expands the CRB1 mutation spectrum of RP in the Chinese population and emphasizes the causative role of CRB1 in RP.

View Figures

View References

1	Bird AC: Retinal photoreceptor dystrophies LI. Edward Jackson Memorial Lecture. Am J Ophthalmol. 119:543–562. 1995. View Article : Google Scholar : PubMed/NCBI
2	Hartong DT, Berson EL and Dryja TP: Retinitis pigmentosa. Lancet. 368:1795–1809. 2006. View Article : Google Scholar : PubMed/NCBI
3	Rivolta C, Sharon D, DeAngelis MM and Dryja TP: Retinitis pigmentosa and allied diseases: Numerous diseases, genes, and inheritance patterns. Hum Mol Genet. 11:1219–1227. 2002. View Article : Google Scholar : PubMed/NCBI
4	Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, Shaffer T, Wong M, Bhattacharjee A, Eichler EE, et al: Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 461:272–276. 2009. View Article : Google Scholar : PubMed/NCBI
5	Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, et al: Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 42:30–35. 2010. View Article : Google Scholar : PubMed/NCBI
6	Neveling K, Collin RW, Gilissen C, van Huet RA, Visser L, Kwint MP, Gijsen SJ, Zonneveld MN, Wieskamp N, de Ligt J, et al: Next-generation genetic testing for retinitis pigmentosa. Hum Mutat. 33:963–972. 2012. View Article : Google Scholar : PubMed/NCBI
7	O'Sullivan J, Mullaney BG, Bhaskar SS, Dickerson JE, Hall G, O'Grady A, Webster A, Ramsden SC and Black GC: A paradigm shift in the delivery of services for diagnosis of inherited retinal disease. J Med Genet. 49:322–326. 2012. View Article : Google Scholar : PubMed/NCBI
8	Katagiri S, Akahori M, Sergeev Y, Yoshitake K, Ikeo K, Furuno M, Hayashi T, Kondo M, Ueno S, Tsunoda K, et al: Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa. PLoS One. 9:e1087212014. View Article : Google Scholar : PubMed/NCBI
9	Wu J, Chen L, Tam OS, Huang XF, Pang CP and Jin ZB: Whole exome sequencing reveals genetic predisposition in a large family with retinitis pigmentosa. Biomed Res Int. 2014:3024872014. View Article : Google Scholar : PubMed/NCBI
10	Villanueva A, Willer JR, Bryois J, Dermitzakis ET, Katsanis N and Davis EE: Whole exome sequencing of a dominant retinitis pigmentosa family identifies a novel deletion in PRPF31. Invest Ophthalmol Vis Sci. 55:2121–2129. 2014. View Article : Google Scholar : PubMed/NCBI
11	Zhou Y, Shuai P, Li X, Wang J, Yang Y, Hao F, Lin H, Zhang D and Gong B: Association of SOD2 polymorphisms with primary open angle glaucoma in a Chinese population. Ophthalmic Genet. 36:43–49. 2015. View Article : Google Scholar : PubMed/NCBI
12	den Hollander AI, ten Brink JB, de Kok YJ, van Soest S, van den Born LI, van Driel MA, van de Pol DJ, Payne AM, Bhattacharya SS, Kellner U, et al: Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12). Nat Genet. 23:217–221. 1999. View Article : Google Scholar : PubMed/NCBI
13	Slavotinek AM: The family of crumbs genes and human disease. Mol Syndromol. 7:274–281. 2016. View Article : Google Scholar : PubMed/NCBI
14	Cordovez JA, Traboulsi EI, Capasso JE, Sadagopan KA, Ganesh A, Rychwalski PJ, Neely KA, Brodie SE and Levin AV: Retinal dystrophy with intraretinal cystoid spaces associated with mutations in the crumbs homologue (CRB1) gene. Ophthalmic Genet. 36:257–264. 2015. View Article : Google Scholar : PubMed/NCBI
15	Booij JC, Florijn RJ, ten Brink JB, Loves W, Meire F, van Schooneveld MJ, de Jong PT and Bergen AA: Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. J Med Genet. 42:e672005. View Article : Google Scholar : PubMed/NCBI
16	Beryozkin A, Zelinger L, Bandah-Rozenfeld D, Harel A, Strom TA, Merin S, Chowers I, Banin E and Sharon D: Mutations in CRB1 are a relatively common cause of autosomal recessive early-onset retinal degeneration in the Israeli and Palestinian populations. Invest Ophthalmol Vis Sci. 54:2068–2075. 2013. View Article : Google Scholar : PubMed/NCBI
17	Chen Y, Lin Y, Vithana EN, Jia L, Zuo X, Wong TY, Chen LJ, Zhu X, Tam PO, Gong B, et al: Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma. Nat Genet. 46:1115–1119. 2014. View Article : Google Scholar : PubMed/NCBI
18	Richard M, Roepman R, Aartsen WM, van Rossum AG, den Hollander AI, Knust E, Wijnholds J and Cremers FP: Towards understanding CRUMBS function in retinal dystrophies. Hum Mol Genet. 15:R235–R243. 2006. View Article : Google Scholar : PubMed/NCBI
19	den Hollander AI, Johnson K, de Kok YJ, Klebes A, Brunner HG, Knust E and Cremers FP: CRB1 has a cytoplasmic domain that is functionally conserved between human and Drosophila. Hum Mol Genet. 10:2767–2773. 2001. View Article : Google Scholar : PubMed/NCBI
20	Tepass U: Crumbs, a component of the apical membrane, is required for zonula adherens formation in primary epithelia of Drosophila. Dev Biol. 177:217–225. 1996. View Article : Google Scholar : PubMed/NCBI
21	Pellikka M, Tanentzapf G, Pinto M, Smith C, McGlade CJ, Ready DF and Tepass U: Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis. Nature. 416:143–149. 2002. View Article : Google Scholar : PubMed/NCBI
22	Beheshtian M, Saee Rad S, Babanejad M, Mohseni M, Hashemi H, Eshghabadi A, Hajizadeh F, Akbari MR, Kahrizi K, Riazi Esfahani M and Najmabadi H: Impact of whole exome sequencing among Iranian patients with autosomal recessive retinitis pigmentosa. Arch Iran Med. 18:776–785. 2015.PubMed/NCBI
23	Thompson DA, Janecke AR, Lange J, Feathers KL, Hübner CA, McHenry CL, Stockton DW, Rammesmayer G, Lupski JR, Antinolo G, et al: Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle. Hum Mol Genet. 14:3865–3875. 2005. View Article : Google Scholar : PubMed/NCBI
24	Bujakowska K, Audo I, Mohand-Saïd S, Lancelot ME, Antonio A, Germain A, Léveillard T, Letexier M, Saraiva JP, Lonjou C, et al: CRB1 mutations in inherited retinal dystrophies. Hum Mutat. 33:306–315. 2012. View Article : Google Scholar : PubMed/NCBI
25	Mehalow AK, Kameya S, Smith RS, Hawes NL, Denegre JM, Young JA, Bechtold L, Haider NB, Tepass U, Heckenlively JR, et al: CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina. Hum Mol Genet. 12:2179–2189. 2003. View Article : Google Scholar : PubMed/NCBI
26	Zhou Y, Tao S, Chen H, Huang L, Zhu X, Li Y, Wang Z, Lin H, Hao F, Yang Z, et al: Exome sequencing analysis identifies compound heterozygous mutation in ABCA4 in a Chinese family with Stargardt disease. PLoS One. 9:e919622014. View Article : Google Scholar : PubMed/NCBI
27	Wang H, Wang X, Zou X, Xu S, Li H, Soens ZT, Wang K, Li Y, Dong F, Chen R and Sui R: Comprehensive molecular diagnosis of a large Chinese Leber congenital Amaurosis cohort. Invest Ophthalmol Vis Sci. 56:3642–3655. 2015. View Article : Google Scholar : PubMed/NCBI