Analysis of mutations of disease-causing gene and the inheritance in sporadic retinitis pigmentosa_Chinese Journal of Ocular Fundus Diseases

Authors：

GuoHuiqing ,  ShengXunlun

Ningxia People's Hospital, Ningxia Eye Hospital, Ningxia 750004, China;

Corresponding author：

ShengXunlun, Email: shengxunlun@163.com

Keywords：

Retinitis pigmentosa/genetics; Inheritance patterns; Genes; Mutation; High-throughput nucleotide sequencing

DOI：

10.3760/cma.j.issn.1005-1015.2016.06.004

Video：

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Objective To observe the disease-causing genes and the inheritance in sporadic retinitis pigmentosa (sRP) in Ningxia region. Methods 49 sRP patients and 128 family members were recruited for this study. All the patients and family members received complete ophthalmic examinations including best corrected visual acuity, slit-lamp microscope, indirect ophthalmoscopy, fundus color photography, visual field, optic coherence tomography, full view electroretinogram. DNA was extracted from patients and family members. Using exon combined target region capture sequencing chip to screen the 230 candidate disease-causing gene mutations, polymerase chain reaction and direct sequencing were used to confirm the disease-causing mutations. Results 24/49 patients (49.0%) had identified disease-causing genes, totally 16 genes were involved. There were 41 mutation sites were found, including 32 new mutations (78.0%). The disease-causing genes include USH2A, C2orf71, GNGA1, RPGR1, IFT140, TULP1, CLRN1, RPE65, ABCA4, GUCA1, EYS, CYP4V2, GPR98 and ATXN7. Based on pedigree analysis, 20 patients were autosomal recessive retinitis pigmentosa, 3 patients were autosomal dominant retinitis pigmentosa and 1 patient was X linked retinitis pigmentosa. 3/7 patients with USH2A mutations were identified as Usher syndrome. Conclusions USHZA is the main disease-causing of sRP patients in Ningxia region. 83.3% of sRP in this cohort are autosomal recessive retinitis pigmentosa.

Citation： GuoHuiqing, ShengXunlun. Analysis of mutations of disease-causing gene and the inheritance in sporadic retinitis pigmentosa. Chinese Journal of Ocular Fundus Diseases, 2016, 32(6): 576-581. doi: 10.3760/cma.j.issn.1005-1015.2016.06.004 Copy

1.	Zobor D, Zrenner E.Retinitis pigmentosa--a review:pathogenesis, guidelines for diagnostics and perspectives[J].Ophthalmologe, 2012, 109(5):501-514.DOI:10.1007/s00347-012-2555-6.
2.	Konieczka K, Flammer AJ, Todorova M, et al. Retinitis pigmentosa and ocular blood flow[J]. EPMA J, 2012, 3(1):17. DOI:10.1186/1878-5085-3-17.
3.	Peterlin B, Canki-Klain N, Morela V, et al. Prevalence of retinitis pigmentosa in Slovenia[J].Clin Genet, 1992, 42(3):122-123.
4.	Xu L, Hu L, Ma K, et al. Prevalence of retinitis pigmentosa in urban and rural adult Chinese:the Beijing Eye Study[J]. Eur J Ophthalmol, 2006, 16(6):865-866.
5.	Dad S, Rendtorff ND, Kann E, et al. Partial USH2A deletions contribute to Usher syndrome in Denmark[J]. Eur J Hum Genet, 2015, 23(12):1750. DOI:10.1038/ejhg.2015.131.
6.	李鹏程, 刘飞, 张明昌, 等.一个Usher综合征家系USH2A基因的突变分析[J].中华医学遗传学杂志, 2015, 32(4):468-471.DOI:10.3760/cma.j.issn.1003-9406.2015.04.003.Li PC, Liu F, Zhang MC, et al.Analysis of USH2A gene mutation in a Chinese family affected with Usher syndrome[J].Chin J Med Genet, 2015, 32(4):468-471.DOI:10.3760/cma.j.issn.1003-9406.2015.04.003.
7.	Rivolta C, Sharon D, DeAngelis MM, et al. Retinitis pigmentosa and allied diseases:numerous diseases, genes, and inheritance patterns[J]. Hum Mol Genet, 2002, 11(10):1219-1227.
8.	Fishman GA. Retinitis pigmentosa:genetic percentages[J]. Arch Ophthalmol, 1978, 96(5):822-826.
9.	庄小娥, 王少元.目标序列捕获测序技术及其在疾病相关基因研究中的作用[J].国际遗传学杂志, 2011, 34(2):102-106.DOI:10.3760/cma.j.issn.1673-4386.2011.02.009.Zhuang XE, Wang SY.Target sequence capture sequencing technology and its application in disease-related gene research[J].Int J Genet, 2011, 34(2):102-106.DOI:10.3760/cma.j.issn. 1673-4386.2011.02.009.
10.	Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa[J]. Lancet, 2006, 368(9549):1795-1809.
11.	Beheshtian M, Saee Rad S, Babanejad M, et al. Impact of whole exome sequencing among Iranian patients with autosomal recessive retinitis pigmentosa[J].Arch Iran Med, 2015, 18(11):776-785.
12.	闫光辉, 盛迅伦, 李自立, 等.110例视网膜色素变性患者RP1基因突变的检测分析[J].中华实验眼科杂志, 2011, 29(11):1005-1009.DOI:10.3760/cma.j.issn.2095-0160.2011.11.013.Yan GH, Sheng XL, Li ZL, et al.Mutations analysis of RP1 gene in 110 Chinese with retinitis pigmentosa[J].Chin J Exp Ophthalmol, 2011, 29(11):1005-1009.1111111155555555j.issn. 2095-0160.2011.11.013.
13.	Katagiri S, Akahori M, Sergeev Y, et al. Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa[J/OL]. PLoS One, 2014, 9(9):108721[2014-09-30].http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182560/. DOI:10.1371/journal.pone.0108721.
14.	Littink KW, van den Born LI, Koenekoop RK, et al. Mutations in the EYS gene account for approximately 5% of autosomal recessive retinitis pigmentosa and cause a fairly homogeneous phenotype[J]. Ophthalmology, 2010, 117(10):2026-2033. DOI:10.1016/j.ophtha.2010.01.040.
15.	Xu W, Dai H, Lu T, et al. Seven novel mutations in the long isoform of the USH2A gene in Chinese families with nonsyndromic retinitis pigmentosa and Usher syndrome type Ⅱ[J]. Mol Vis, 2011, 17:1537-1552.
16.	Seyedahmadi BJ, Rivolta C, Keene JA, et al. Comprehensive screening of the USH2A gene in Usher syndrome type Ⅱand non-syndromic recessive retinitis pigmentosa[J]. Exp Eye Res, 2004, 79(2):167-173.
17.	Khateb S, Zelinger L, Ben-Yosef T, et al. Exome sequencing identifies a founder frameshift mutation in an alternative exon of USH1C as the cause of autosomal recessive retinitis pigmentosa with late-onset hearing loss[J/OL].PLoS One, 2012, 7(12):51566[2012-12-12]. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520954/. DOI:10.1371/journal.pone.0051566.
18.	Mataftsi A, Zografos L, Millá E, et al. Bietti's crystalline corneoretinal dystrophy:a cross-sectional study[J]. Retina, 2004, 24(3):416-426.
19.	单明华, 李扬.结晶样视网膜色素变性CYP4V2基因突变分析[D].北京:首都医科大学, 2006.Shan MH, Li Y.CYP4V2 mutation analysis of crystalline retinitis pigmentosa[D].Beijing:Capital Medical University, 2006.
20.	Lobo GP, Ebke LA, Au A, et al. TULP1 missense mutations induces the endoplasmic reticulum unfolded protein response stress complex (ER-UPR)[J]. Adv Exp Med Biol, 2016, 854:223-230. DOI:10.1007/978-3-319-17121-0_30.

1. Zobor D, Zrenner E.Retinitis pigmentosa--a review:pathogenesis, guidelines for diagnostics and perspectives[J].Ophthalmologe, 2012, 109(5):501-514.DOI:10.1007/s00347-012-2555-6.
2. Konieczka K, Flammer AJ, Todorova M, et al. Retinitis pigmentosa and ocular blood flow[J]. EPMA J, 2012, 3(1):17. DOI:10.1186/1878-5085-3-17.
3. Peterlin B, Canki-Klain N, Morela V, et al. Prevalence of retinitis pigmentosa in Slovenia[J].Clin Genet, 1992, 42(3):122-123.
4. Xu L, Hu L, Ma K, et al. Prevalence of retinitis pigmentosa in urban and rural adult Chinese:the Beijing Eye Study[J]. Eur J Ophthalmol, 2006, 16(6):865-866.
5. Dad S, Rendtorff ND, Kann E, et al. Partial USH2A deletions contribute to Usher syndrome in Denmark[J]. Eur J Hum Genet, 2015, 23(12):1750. DOI:10.1038/ejhg.2015.131.
6. 李鹏程, 刘飞, 张明昌, 等.一个Usher综合征家系USH2A基因的突变分析[J].中华医学遗传学杂志, 2015, 32(4):468-471.DOI:10.3760/cma.j.issn.1003-9406.2015.04.003.Li PC, Liu F, Zhang MC, et al.Analysis of USH2A gene mutation in a Chinese family affected with Usher syndrome[J].Chin J Med Genet, 2015, 32(4):468-471.DOI:10.3760/cma.j.issn.1003-9406.2015.04.003.
7. Rivolta C, Sharon D, DeAngelis MM, et al. Retinitis pigmentosa and allied diseases:numerous diseases, genes, and inheritance patterns[J]. Hum Mol Genet, 2002, 11(10):1219-1227.
8. Fishman GA. Retinitis pigmentosa:genetic percentages[J]. Arch Ophthalmol, 1978, 96(5):822-826.
9. 庄小娥, 王少元.目标序列捕获测序技术及其在疾病相关基因研究中的作用[J].国际遗传学杂志, 2011, 34(2):102-106.DOI:10.3760/cma.j.issn.1673-4386.2011.02.009.Zhuang XE, Wang SY.Target sequence capture sequencing technology and its application in disease-related gene research[J].Int J Genet, 2011, 34(2):102-106.DOI:10.3760/cma.j.issn. 1673-4386.2011.02.009.
10. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa[J]. Lancet, 2006, 368(9549):1795-1809.
11. Beheshtian M, Saee Rad S, Babanejad M, et al. Impact of whole exome sequencing among Iranian patients with autosomal recessive retinitis pigmentosa[J].Arch Iran Med, 2015, 18(11):776-785.
12. 闫光辉, 盛迅伦, 李自立, 等.110例视网膜色素变性患者RP1基因突变的检测分析[J].中华实验眼科杂志, 2011, 29(11):1005-1009.DOI:10.3760/cma.j.issn.2095-0160.2011.11.013.Yan GH, Sheng XL, Li ZL, et al.Mutations analysis of RP1 gene in 110 Chinese with retinitis pigmentosa[J].Chin J Exp Ophthalmol, 2011, 29(11):1005-1009.1111111155555555j.issn. 2095-0160.2011.11.013.
13. Katagiri S, Akahori M, Sergeev Y, et al. Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa[J/OL]. PLoS One, 2014, 9(9):108721[2014-09-30].http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182560/. DOI:10.1371/journal.pone.0108721.
14. Littink KW, van den Born LI, Koenekoop RK, et al. Mutations in the EYS gene account for approximately 5% of autosomal recessive retinitis pigmentosa and cause a fairly homogeneous phenotype[J]. Ophthalmology, 2010, 117(10):2026-2033. DOI:10.1016/j.ophtha.2010.01.040.
15. Xu W, Dai H, Lu T, et al. Seven novel mutations in the long isoform of the USH2A gene in Chinese families with nonsyndromic retinitis pigmentosa and Usher syndrome type Ⅱ[J]. Mol Vis, 2011, 17:1537-1552.
16. Seyedahmadi BJ, Rivolta C, Keene JA, et al. Comprehensive screening of the USH2A gene in Usher syndrome type Ⅱand non-syndromic recessive retinitis pigmentosa[J]. Exp Eye Res, 2004, 79(2):167-173.
17. Khateb S, Zelinger L, Ben-Yosef T, et al. Exome sequencing identifies a founder frameshift mutation in an alternative exon of USH1C as the cause of autosomal recessive retinitis pigmentosa with late-onset hearing loss[J/OL].PLoS One, 2012, 7(12):51566[2012-12-12]. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520954/. DOI:10.1371/journal.pone.0051566.
18. Mataftsi A, Zografos L, Millá E, et al. Bietti's crystalline corneoretinal dystrophy:a cross-sectional study[J]. Retina, 2004, 24(3):416-426.
19. 单明华, 李扬.结晶样视网膜色素变性CYP4V2基因突变分析[D].北京:首都医科大学, 2006.Shan MH, Li Y.CYP4V2 mutation analysis of crystalline retinitis pigmentosa[D].Beijing:Capital Medical University, 2006.
20. Lobo GP, Ebke LA, Au A, et al. TULP1 missense mutations induces the endoplasmic reticulum unfolded protein response stress complex (ER-UPR)[J]. Adv Exp Med Biol, 2016, 854:223-230. DOI:10.1007/978-3-319-17121-0_30.

Chinese Journal of Ocular Fundus Diseases

Analysis of mutations of disease-causing gene and the inheritance in sporadic retinitis pigmentosa

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