Current research in the genes and proteins related with Usher syndrome_Chinese Journal of Ocular Fundus Diseases

Authors：

GaoJinzhan ,  MaXiang

Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China;

Corresponding author：

MaXiang, Email: xma9467@vip.sina.com

Keywords：

Usher syndromes; Retinitis pigmentosa; Genes, recessive; Mutation; Egg white; Review

DOI：

10.3760/cma.j.issn.1005-1015.2016.03.031

Video：

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Usher syndrome (USH) is an autosomal recessive hereditary disease, characterized as retinitis pigmentosa and deafness. According to the severity of hearing loss, presence or absence of vestibular dysfunction, Usher syndrome is divided into 3 clinical subtypes: USH1, USH2 and USH3. Due to the genetically heterogeneous, it is important and valuable to find out the gene mutations in USH patients, which will be helpful to prenatal diagnosis, early intervention and gene therapy. Till now, the following 13 USH-related chromosomal loci were reported in the literature: USH1B, USH1C, USH1D (CDH23 gene), USH1F (PCDH15 gene), USH1G (SANS gene), USH1E, USH1H, USH1J and USH1K, USH2A, USH2C, USH2D and USH3 (CLRN1 gene). Ten out of all 13 loci have been located and identified. But more mechanisms should be further investigated, such as the relationship between the locus of gene mutations and clinical symptoms, how the modified protein structures and functions trigger clinical symptoms.

Citation： GaoJinzhan, MaXiang. Current research in the genes and proteins related with Usher syndrome. Chinese Journal of Ocular Fundus Diseases, 2016, 32(3): 342-346. doi: 10.3760/cma.j.issn.1005-1015.2016.03.031 Copy

1.	Bonnet C, El-Amraoui A. Usher syndrome (sensorineural deafness and retinitis pigmentosa):pathogenesis[J]. Curr Opin Neurol, 2012, 25(1):42-49.DOI:10.1097/WCO.0b013e32834ef8b2.
2.	Bonnet C, Grati M, Marlin S, et al. Complete exon sequencing of all known Usher syndrome genes greatly improves[J]. Orphanet J Rare Dis, 2011, 6:21. DOI:10.1186/1750-1172-6-21.
3.	Yan D, Liu XZ. Genetics and pathological mechanisms of Usher syndrome[J]. J Hum Genet, 2010, 55(6):327-335.DOI:10.1038/jhg.2010.29.
4.	Friedman TB, Schultz JM, Ahmed ZM, et al. Usher syndrome:hearing loss with vision loss[J]. Adv Otorhinolaryngol, 2011, 70:56-65.DOI:10.1159/000322473.
5.	Vanda SL, Daniel G, Richard TL, et al. The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid enzyme, RPE65[J]. Hum Mol Genet, 2011, 20(13):2560-2570.DOI:10.1093/hmq/ddr155.
6.	Wei X, Sun Y, Xie J, et al. Next-generation sequencing identifies a novel compound heterozygous mutation in a Chinese patient with Usher syndrome 1B[J]. Clin Chim Acta, 2012, 413(23-24):1866-1871.DOI:10.1016/j.cca.2012.07.022.
7.	Hideki M, Naohiro S, Atsushi S, et al. Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patient:a cross-sectional, multi-center next-generation sequencing study[J]. Orphanet J Rare Dis, 2013, 8:172. DOI:10.1186/1750-1172-8-172.
8.	Wei Z, Xin J, Yan G, et al. Phenotype of Usher syndrome typeⅡassociated with compound missense mutations of c.721C>T and c.1969 C>T in MYO7A in a Chinese Usher syndrome family[J]. Int J Ophthalmol, 2015, 8(4):670-674.DOI:10.3980/j.issn.2222-3959.2015.04.05.
9.	Roux AF, Faugere V, Vache C, et al. Four-year follow-up of diagnostic service in USH1 patients[J]. Invest Ophthalmol Vis Sci, 2011, 52(7):4063-4071.DOI:10.1167/iovs.10-6869.
10.	Leah R, Christine S, Stavit A, et al. Novel mutations of MYO7A and USH1G in Israeli Arab families with Usher syndrome type 1[J]. Mol Vis, 2011, 17:3548-3555.
11.	Fei L, Pengcheng L, Ying L, et al. Novel compound heterozygous mutations in MYO7A in a Chinese family with Usher syndrome type 1[J]. Mol Vis, 2013, 19:695-701.
12.	Polona LQS, Zubin S, Nell R, et al. Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study[J]. J Med Genet, 2012, 49(1):27-36.DOI:10.1136/jmedgenet-2011-100468.
13.	Maria JA, Gema GG, Teresa J, et al. Novel mutations in the USH1C gene in Usher syndrome patients[J]. Mol Vis, 2010, 16:2948-2954.
14.	Julie MS, Rashid B, Anne CM, et al. Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes[J]. J Med Genet, 2011, 48(11):767-775.DOI:10.1136/jmedgenet-2011-100262.
15.	Nakanishi H, Ohtsubo M, Iwasaki S, et al. Mutation analysis of the MYO7A and CDH23 genes in Japanese patients with Usher syndrome type 1[J]. J Hum Genet, 2010, 55(12):796-800.DOI:10.1038/jhg.2010.115.
16.	Elena A, Teresa J, Gema GG, et al. Identification of large rearrangements of the PCDH15 gene by combined MLPA and a CGH:large duplications are responsible for Usher syndrome[J]. Invest Ophthalmol Vis Sci, 2010, 51(11):5480-5485.DOI:10.1167/iovs.10-5359.
17.	Faiqa I, Khalid T, Ghada BK, et al. USH1G with unique retinal findings caused by a novel truncating mutation identified by genome-wide linkage analysis[J]. Mol Vis, 2012, 18:1885-1894.
18.	Hassan C, Josseline K, Sylvie G, et al. A newly identified locus for Usher syndrome typeⅠ, USH1E, maps to chromosome 21q21[J]. Hum Mol Genet, 1997, 6(1):27-31.
19.	Zubair MA, Saima R, Shaheen NK, et al. USH1H, a novel locus for typeⅠUsher syndrome, maps to chromosome 15q22-23[J]. Clin Genet, 2009, 75(1):86-91.DOI:10.1111/j.1399-0004.2008.01038.x.
20.	Riazuddin S, Belyantseva IA, Giese AP, et al. Alterations of the CIB2 calcium-and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafess DFNB48[J]. Nat Genet, 2012, 44(11):1265-1271.DOI:10.1038/ng.2426.
21.	Thomas JJ, Rashid B, Naureen L, et al. USH1K, a novel locus for typeⅠUsher syndrome, maps to chromosome 10p11.21-q21.1[J]. J Hum Genet, 2012, 57(10):633-637.DOI:10.1038/jhg.2012.79.
22.	Eva L, Zubin S, Maria BG, et al. The effect of the common c.2299delG mutation in USH2A on RNA splicing[J]. Exp Eye Res, 2014, 122:9-12.DOI:10.1016/j.exer.2014.02.018.
23.	Baux D, Larrieu L, Blanchet C, et al. Molecular and in silico analyses of the full-length isoform of usherin identify new pathogenic alleles in Usher typeⅡpatients[J]. Hum Mutat, 2007, 28(8):781-789.DOI:10.1002/humu.20513.
24.	Hiroshi N, Masafumi O, Satoshi I, et al. Novel USH2A mutations in Japanese Usher syndrome type 2 patients:marked differences in the mutation spectrum between the Japanese and other populations[J]. J Hum Genet, 2011, 56(7):484-490.DOI:10.1038/jhg.2011.45.
25.	Gema GG, Maria JA, Teresa J, et al. Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutation[J]. Orphanet J Rare Dis, 2011, 6(65):1750-1172.DOI:10.1186/1750-1172-6-65.
26.	Jaijo T, Aller E, Aparisi MJ, et al. Functional analysis of splicing mutations in MYO7A and USH2A genes[J]. Clin Genet, 2011, 79(3):282-288.DOI:10.1111/j.1399-0004.2010.01454.x.
27.	Terri LM, Babak JS, Meradith O, et al. Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome typeⅡor non-syndromic retinitis pigmentosa[J]. J Med Genet, 2010, 47(7):499-506.DOI:10.1136/jmg.2009.075143.
28.	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 typeⅡ[J]. Mol Vis, 2011, 17:1537-1552.
29.	Hairong S, Huai B, Yangchun P, et al. Targeted exome sequencing reveals novel USH2A mutation in Chinese patients with simplex Usher syndrome[J]. BMC Med Genet, 2015, 16:83.DOI:10.1186/s12881-015-0223-9.
30.	Henning F, Jorg B, Katrin P, et al. A genetic basis for mechanosensory traits in humans[J/OL]. PLoS Biol, 2012, 10(5):1001318[2012-05-01]. http://dx.plos.org/10.1371/journal.pbio.1001318. DOI:10.1371/journal.pbio.1001318.
31.	Sun JP, Li R, Ren HZ, et al. The very large G protein coupled receptor (Vlgr1) in hair cells[J]. J Mol Neurosci, 2013, 50(1):204-214.DOI:10.1007/s12031-012-9911-5.
32.	Inga E, Jennifer BP, Max C, et al. PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome[J]. J Clin Invest, 2010, 120(6):1812-1823.DOI:10.1172/JCI39715.
33.	Gema GG, Thomas B, David B, et al. The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort[J]. Mol Vis, 2013, 19:367-373.
34.	Astra D, Rachel MS, Wentao D, et al. AAV-mediated clarin-1 expression in the mouse retina:implications for USH3A gene therapy[J]. PLoS One, 2016, 11(2):0148874[2016-02-16].http://dx.plos.org/10.1371/journal.pone.0148874. DOI:10.1371/journal.pone.0148874.
35.	Ruishuang G, Sami M, Daniel HC, et al. The mechanosensory structure of the hair cell requires clarin-1, a protein encoded by Usher syndromeⅢcausative gene[J]. J Neurosci, 2012, 32(28):9485-9498.DOI:10.1523/JNEUROSCI.0311-12.2012.
36.	Akoury E, El ZE, Mansour A, et al. A novel 5-bp deletion in clarin 1 in a family with Usher syndrome[J]. Ophthalmic Genet, 2011, 32(4):245-249.DOI:10.1167/iovs.09-5109.
37.	Kavitha R, Hanna V, Austin R, et al. Cone structure in patients with usher syndrome typeⅢand mutations in the clarin 1 gene[J]. JAMA Ophthalmol, 2013, 131(1):67-74. DOI:10.1001/2013.jamaophthalmol.2.
38.	Gema GG, Maria JA, Regina R, et al. Two novel disease-causing mutations in the CLRN1 gene in patients with Usher syndrome type 3[J]. Mol Vis, 2012, 18:3070-3078.

1. Bonnet C, El-Amraoui A. Usher syndrome (sensorineural deafness and retinitis pigmentosa):pathogenesis[J]. Curr Opin Neurol, 2012, 25(1):42-49.DOI:10.1097/WCO.0b013e32834ef8b2.
2. Bonnet C, Grati M, Marlin S, et al. Complete exon sequencing of all known Usher syndrome genes greatly improves[J]. Orphanet J Rare Dis, 2011, 6:21. DOI:10.1186/1750-1172-6-21.
3. Yan D, Liu XZ. Genetics and pathological mechanisms of Usher syndrome[J]. J Hum Genet, 2010, 55(6):327-335.DOI:10.1038/jhg.2010.29.
4. Friedman TB, Schultz JM, Ahmed ZM, et al. Usher syndrome:hearing loss with vision loss[J]. Adv Otorhinolaryngol, 2011, 70:56-65.DOI:10.1159/000322473.
5. Vanda SL, Daniel G, Richard TL, et al. The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid enzyme, RPE65[J]. Hum Mol Genet, 2011, 20(13):2560-2570.DOI:10.1093/hmq/ddr155.
6. Wei X, Sun Y, Xie J, et al. Next-generation sequencing identifies a novel compound heterozygous mutation in a Chinese patient with Usher syndrome 1B[J]. Clin Chim Acta, 2012, 413(23-24):1866-1871.DOI:10.1016/j.cca.2012.07.022.
7. Hideki M, Naohiro S, Atsushi S, et al. Diverse spectrum of rare deafness genes underlies early-childhood hearing loss in Japanese patient:a cross-sectional, multi-center next-generation sequencing study[J]. Orphanet J Rare Dis, 2013, 8:172. DOI:10.1186/1750-1172-8-172.
8. Wei Z, Xin J, Yan G, et al. Phenotype of Usher syndrome typeⅡassociated with compound missense mutations of c.721C>T and c.1969 C>T in MYO7A in a Chinese Usher syndrome family[J]. Int J Ophthalmol, 2015, 8(4):670-674.DOI:10.3980/j.issn.2222-3959.2015.04.05.
9. Roux AF, Faugere V, Vache C, et al. Four-year follow-up of diagnostic service in USH1 patients[J]. Invest Ophthalmol Vis Sci, 2011, 52(7):4063-4071.DOI:10.1167/iovs.10-6869.
10. Leah R, Christine S, Stavit A, et al. Novel mutations of MYO7A and USH1G in Israeli Arab families with Usher syndrome type 1[J]. Mol Vis, 2011, 17:3548-3555.
11. Fei L, Pengcheng L, Ying L, et al. Novel compound heterozygous mutations in MYO7A in a Chinese family with Usher syndrome type 1[J]. Mol Vis, 2013, 19:695-701.
12. Polona LQS, Zubin S, Nell R, et al. Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study[J]. J Med Genet, 2012, 49(1):27-36.DOI:10.1136/jmedgenet-2011-100468.
13. Maria JA, Gema GG, Teresa J, et al. Novel mutations in the USH1C gene in Usher syndrome patients[J]. Mol Vis, 2010, 16:2948-2954.
14. Julie MS, Rashid B, Anne CM, et al. Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes[J]. J Med Genet, 2011, 48(11):767-775.DOI:10.1136/jmedgenet-2011-100262.
15. Nakanishi H, Ohtsubo M, Iwasaki S, et al. Mutation analysis of the MYO7A and CDH23 genes in Japanese patients with Usher syndrome type 1[J]. J Hum Genet, 2010, 55(12):796-800.DOI:10.1038/jhg.2010.115.
16. Elena A, Teresa J, Gema GG, et al. Identification of large rearrangements of the PCDH15 gene by combined MLPA and a CGH:large duplications are responsible for Usher syndrome[J]. Invest Ophthalmol Vis Sci, 2010, 51(11):5480-5485.DOI:10.1167/iovs.10-5359.
17. Faiqa I, Khalid T, Ghada BK, et al. USH1G with unique retinal findings caused by a novel truncating mutation identified by genome-wide linkage analysis[J]. Mol Vis, 2012, 18:1885-1894.
18. Hassan C, Josseline K, Sylvie G, et al. A newly identified locus for Usher syndrome typeⅠ, USH1E, maps to chromosome 21q21[J]. Hum Mol Genet, 1997, 6(1):27-31.
19. Zubair MA, Saima R, Shaheen NK, et al. USH1H, a novel locus for typeⅠUsher syndrome, maps to chromosome 15q22-23[J]. Clin Genet, 2009, 75(1):86-91.DOI:10.1111/j.1399-0004.2008.01038.x.
20. Riazuddin S, Belyantseva IA, Giese AP, et al. Alterations of the CIB2 calcium-and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafess DFNB48[J]. Nat Genet, 2012, 44(11):1265-1271.DOI:10.1038/ng.2426.
21. Thomas JJ, Rashid B, Naureen L, et al. USH1K, a novel locus for typeⅠUsher syndrome, maps to chromosome 10p11.21-q21.1[J]. J Hum Genet, 2012, 57(10):633-637.DOI:10.1038/jhg.2012.79.
22. Eva L, Zubin S, Maria BG, et al. The effect of the common c.2299delG mutation in USH2A on RNA splicing[J]. Exp Eye Res, 2014, 122:9-12.DOI:10.1016/j.exer.2014.02.018.
23. Baux D, Larrieu L, Blanchet C, et al. Molecular and in silico analyses of the full-length isoform of usherin identify new pathogenic alleles in Usher typeⅡpatients[J]. Hum Mutat, 2007, 28(8):781-789.DOI:10.1002/humu.20513.
24. Hiroshi N, Masafumi O, Satoshi I, et al. Novel USH2A mutations in Japanese Usher syndrome type 2 patients:marked differences in the mutation spectrum between the Japanese and other populations[J]. J Hum Genet, 2011, 56(7):484-490.DOI:10.1038/jhg.2011.45.
25. Gema GG, Maria JA, Teresa J, et al. Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutation[J]. Orphanet J Rare Dis, 2011, 6(65):1750-1172.DOI:10.1186/1750-1172-6-65.
26. Jaijo T, Aller E, Aparisi MJ, et al. Functional analysis of splicing mutations in MYO7A and USH2A genes[J]. Clin Genet, 2011, 79(3):282-288.DOI:10.1111/j.1399-0004.2010.01454.x.
27. Terri LM, Babak JS, Meradith O, et al. Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome typeⅡor non-syndromic retinitis pigmentosa[J]. J Med Genet, 2010, 47(7):499-506.DOI:10.1136/jmg.2009.075143.
28. 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 typeⅡ[J]. Mol Vis, 2011, 17:1537-1552.
29. Hairong S, Huai B, Yangchun P, et al. Targeted exome sequencing reveals novel USH2A mutation in Chinese patients with simplex Usher syndrome[J]. BMC Med Genet, 2015, 16:83.DOI:10.1186/s12881-015-0223-9.
30. Henning F, Jorg B, Katrin P, et al. A genetic basis for mechanosensory traits in humans[J/OL]. PLoS Biol, 2012, 10(5):1001318[2012-05-01]. http://dx.plos.org/10.1371/journal.pbio.1001318. DOI:10.1371/journal.pbio.1001318.
31. Sun JP, Li R, Ren HZ, et al. The very large G protein coupled receptor (Vlgr1) in hair cells[J]. J Mol Neurosci, 2013, 50(1):204-214.DOI:10.1007/s12031-012-9911-5.
32. Inga E, Jennifer BP, Max C, et al. PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome[J]. J Clin Invest, 2010, 120(6):1812-1823.DOI:10.1172/JCI39715.
33. Gema GG, Thomas B, David B, et al. The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort[J]. Mol Vis, 2013, 19:367-373.
34. Astra D, Rachel MS, Wentao D, et al. AAV-mediated clarin-1 expression in the mouse retina:implications for USH3A gene therapy[J]. PLoS One, 2016, 11(2):0148874[2016-02-16].http://dx.plos.org/10.1371/journal.pone.0148874. DOI:10.1371/journal.pone.0148874.
35. Ruishuang G, Sami M, Daniel HC, et al. The mechanosensory structure of the hair cell requires clarin-1, a protein encoded by Usher syndromeⅢcausative gene[J]. J Neurosci, 2012, 32(28):9485-9498.DOI:10.1523/JNEUROSCI.0311-12.2012.
36. Akoury E, El ZE, Mansour A, et al. A novel 5-bp deletion in clarin 1 in a family with Usher syndrome[J]. Ophthalmic Genet, 2011, 32(4):245-249.DOI:10.1167/iovs.09-5109.
37. Kavitha R, Hanna V, Austin R, et al. Cone structure in patients with usher syndrome typeⅢand mutations in the clarin 1 gene[J]. JAMA Ophthalmol, 2013, 131(1):67-74. DOI:10.1001/2013.jamaophthalmol.2.
38. Gema GG, Maria JA, Regina R, et al. Two novel disease-causing mutations in the CLRN1 gene in patients with Usher syndrome type 3[J]. Mol Vis, 2012, 18:3070-3078.

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