Mutational frequencies in usherin (USH2A gene) in 26 Colombian individuals with Usher syndrome type II
Keywords:
Usher syndromes/genetics, retinitis pigmentosa, hearing loss, sensorineural, Genetics, DNA mutational analysis, Colombia.
Abstract
Introduction. Usher syndrome is a disorder characterized by progressive retinitis pigmentosa, prelingual sensory hearing loss and vestibular dysfunction. It is the most frequent cause of deaf-blindness in humans. Three clinical types and twelve genetic subtypes have been characterized. Type II is the most common, and among these cases, nearly 80% have mutations in the USH2A gene.Objective. The aim of the study was to establish the mutational frequencies for the short isoform of USH2A gene in Usher syndrome type II.
Materials and methods. Twenty-six Colombian individuals with Usher syndrome type II were included. SSCP analysis for 20 exons of the short isoform was performed and abnormal patterns were sequenced. Sequencing of exon 13 of the USH2A gene was performed for all the individuals because the most frequent mutation is located in this exon.
Results. The most frequent mutation was c.2299delG, identified in the 27% (n=8) of the sample. The second mutation, p.R334W, showed a frequency of 15%. A new variant identified in the 5'UTR region, g.129G>T, was present in 1 individual (4%). Four polymorphisms were identified; one of them is a new deletion in exon 20, first reported in this study.
Conclusions. Mutations in the usherin short isoform were identified in 38% of a sample of 26 USH2 cases. Molecular diagnosis was established in 7 of the 26.
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References
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2. Keats BJ, Corey DP. The usher syndromes. Am J Med Genet. 1999;89:158-66.
3. Hallgren B. Retinitis pigmentosa combined with congenital deafness; with vestibulo-cerebellar ataxia and mental abnormality in a proportion of cases: A clinical and genetico-statistical study. Acta Psychiatr Scand 1959;34(Suppl.):1-101.
4. Tamayo M, Bernal JE, Tamayo GE, Frias JL. Study of the etiology of deafness in an institutionalized population in Colombia. Am J Med Genet. 1992;44:405-8.
5. Tamayo ML, Bernal JE, Tamayo GE, Frias JL, Alvira G, Vergara O, et al. Usher syndrome: Results of a screening program in Colombia. Clin Genet. 1991;40:304-11.
6. Tamayo ML, Maldonado C, Plaza SL, Alvira GM, Tamayo GE, Zambrano M, et al. Neuroradiology and clinical aspects of Usher syndrome. Clin Genet. 1996;50:126-32.
7. Pakarinen L, Tuppurainen K, Laippala P, Mantyjarvi M, Puhakka H. The ophthalmological course of Usher syndrome type III. Int Ophthalmol. 1995;19:307-11.
8. Eudy JD, Weston MD, Yao S, Hoover DM, Rehm HL, Ma-Edmonds M, et al. Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa. Science. 1998;280:1753-7.
9. Liu X, Bulgakov OV, Darrow KN, Pawlyk B, Adamian M, Liberman MC, et al. Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells. Proc Natl Acad Sci USA. 2007;104:4413-8.
10. Hope CI, Bundey S, Proops D, Fielder AR. Usher syndrome in the city of Birmingham--prevalence and clinical classification. Br J Ophthalmol. 1997;81:46-53.
11. Ouyang XM, Hejtmancik JF, Jacobson SG, Li AR, Du LL, Angeli S, et al. Mutational spectrum in Usher syndrome type II. Clin Genet. 2004;65:288-93.
12. Rosenberg T, Haim M, Hauch AM, Parving A. The prevalence of Usher syndrome and other retinal dystrophy-hearing impairment associations. Clin Genet. 1997; 51: 314-21.
13. Pieke-Dahl S, Ohlemiller KK, McGee J, Walsh EJ, Kimberling WJ. Hearing loss in the RBF/DnJ mouse, a proposed animal model of Usher syndrome type IIa. Hear Res. 1997;112:1-12.
14. Weston MD, Eudy JD, Fujita S, Yao S, Usami S, Cremers C, et al. Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa. Am J Hum Genet. 2000;66:1199-210.
15. Aller E, Jaijo T, Beneyto M, Najera C, Oltra S, Ayuso C, et al. Identification of 14 novel mutations in the long isoform of USH2A in Spanish patients with Usher syndrome type II. J Med Genet. 2006;43:e55.
16. Baux D, Larrieu L, Blanchet C, Hamel C, Ben Salah S, Vielle A, et al. Molecular and in silico analyses of the full-length isoform of usherin identify new pathogenic alleles in Usher type II patients. Hum Mutat. 2007;28:781-9.
17. van Wijk E, Pennings RJ, te Brinke H, Claassen A, Yntema HG, Hoefsloot LH, et al. Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II. Am J Hum Genet. 2004;74:738-44.
18. Adato A, Weston MD, Berry A, Kimberling WJ, Bonne-Tamir A. Three novel mutations and twelve polymorphisms identified in the USH2A gene in Israeli USH2 families. Hum Mutat. 2000;15:388.
19. Nelson MR, Marnellos G, Kammerer S, Hoyal CR, Shi MM, Cantor CR, et al. Large-scale validation of single nucleotide polymorphisms in gene regions. Genome Res. 2004;14:1664-8.
20. Spandau UH, Rohrschneider K. Prevalence and geographical distribution of Usher syndrome in Germany. Graefes Arch Clin Exp Ophthalmol. 2002;240:495-8.
21. Bernal S, Ayuso C, Antinolo G, Gimenez A, Borrego S, Trujillo MJ, et al. Mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa: high prevalence and phenotypic variation. J Med Genet. 2003;40:e8.
22. Dreyer B, Tranebjaerg L, Rosenberg T, Weston MD, Kimberling WJ, Nilssen O. Identification of novel USH2A mutations: Implications for the structure of USH2A protein. Eur J Hum Genet. 2000;8:500-6.
23. Leroy BP, Aragón-Martín JA, Weston MD, Bessant DA, Willis C, Webster AR, et al. Spectrum of mutations in USH2A in British patients with Usher syndrome type II. Exp Eye Res. 2001;72:503-9.
24. Beneyto MM, Cuevas JM, Millan JM, Espinos C, Mateu E, González-Cabo P, et al. Prevalence of 2314delG mutation in Spanish patients with Usher syndrome type II (USH2). Ophthalmic Genet. 2000;21:123-8.
25. Maubaret C, Griffoin JM, Arnaud B, Hamel C. Novel mutations in MYO7A and USH2A in Usher syndrome. Ophthalmic Genet. 2005;26:25-9.
26. Dai H, Zhang X, Zhao X, Deng T, Dong B, Wang J, et al. Identification of five novel mutations in the long isoform of the USH2A gene in Chinese families with Usher syndrome type II. Mol Vis. 2008;14:2067-75.
27. McGee TL, Seyedahmadi BJ, Sweeney MO, Dryja TP, Berson EL. Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa. J Med Genet. 2010;47:499-506.
28. Rohlin A, Wernersson J, Engwall Y, Wiklund L, Bjork J, Nordling M. Parallel sequencing used in detection of mosaic mutations: Comparison with four diagnostic DNA screening techniques. Hum Mutat. 2009;30:1012-20.
29. Aller E, Larrieu L, Jaijo T, Baux D, Espinos C, González-Candelas F, et al. The USH2A c.2299delG mutation: Dating its common origin in a Southern European population. Eur J Hum Genet. 2010;18:788-93.
30. Nakanishi H, Ohtsubo M, Iwasaki S, Hotta Y, Mizuta K, Mineta H, et al. Identification of 11 novel mutations in USH2A among Japanese patients with Usher syndrome type 2. Clin Genet. 2009;76:383-91.
31. Dreyer B, Brox V, Tranebjaerg L, Rosenberg T, Sadeghi AM, Moller C, et al. Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II. Hum Mutat. 2008;29:451.
32. Jaijo T, Aller E, García-García G, Aparisi MJ, Bernal S, Ávila-Fernández A, et al. Microarray-based mutation analysis of 183 Spanish families with Usher syndrome. Invest Ophthalmol Vis Sci. 2010;51:1311-7.
2. Keats BJ, Corey DP. The usher syndromes. Am J Med Genet. 1999;89:158-66.
3. Hallgren B. Retinitis pigmentosa combined with congenital deafness; with vestibulo-cerebellar ataxia and mental abnormality in a proportion of cases: A clinical and genetico-statistical study. Acta Psychiatr Scand 1959;34(Suppl.):1-101.
4. Tamayo M, Bernal JE, Tamayo GE, Frias JL. Study of the etiology of deafness in an institutionalized population in Colombia. Am J Med Genet. 1992;44:405-8.
5. Tamayo ML, Bernal JE, Tamayo GE, Frias JL, Alvira G, Vergara O, et al. Usher syndrome: Results of a screening program in Colombia. Clin Genet. 1991;40:304-11.
6. Tamayo ML, Maldonado C, Plaza SL, Alvira GM, Tamayo GE, Zambrano M, et al. Neuroradiology and clinical aspects of Usher syndrome. Clin Genet. 1996;50:126-32.
7. Pakarinen L, Tuppurainen K, Laippala P, Mantyjarvi M, Puhakka H. The ophthalmological course of Usher syndrome type III. Int Ophthalmol. 1995;19:307-11.
8. Eudy JD, Weston MD, Yao S, Hoover DM, Rehm HL, Ma-Edmonds M, et al. Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa. Science. 1998;280:1753-7.
9. Liu X, Bulgakov OV, Darrow KN, Pawlyk B, Adamian M, Liberman MC, et al. Usherin is required for maintenance of retinal photoreceptors and normal development of cochlear hair cells. Proc Natl Acad Sci USA. 2007;104:4413-8.
10. Hope CI, Bundey S, Proops D, Fielder AR. Usher syndrome in the city of Birmingham--prevalence and clinical classification. Br J Ophthalmol. 1997;81:46-53.
11. Ouyang XM, Hejtmancik JF, Jacobson SG, Li AR, Du LL, Angeli S, et al. Mutational spectrum in Usher syndrome type II. Clin Genet. 2004;65:288-93.
12. Rosenberg T, Haim M, Hauch AM, Parving A. The prevalence of Usher syndrome and other retinal dystrophy-hearing impairment associations. Clin Genet. 1997; 51: 314-21.
13. Pieke-Dahl S, Ohlemiller KK, McGee J, Walsh EJ, Kimberling WJ. Hearing loss in the RBF/DnJ mouse, a proposed animal model of Usher syndrome type IIa. Hear Res. 1997;112:1-12.
14. Weston MD, Eudy JD, Fujita S, Yao S, Usami S, Cremers C, et al. Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa. Am J Hum Genet. 2000;66:1199-210.
15. Aller E, Jaijo T, Beneyto M, Najera C, Oltra S, Ayuso C, et al. Identification of 14 novel mutations in the long isoform of USH2A in Spanish patients with Usher syndrome type II. J Med Genet. 2006;43:e55.
16. Baux D, Larrieu L, Blanchet C, Hamel C, Ben Salah S, Vielle A, et al. Molecular and in silico analyses of the full-length isoform of usherin identify new pathogenic alleles in Usher type II patients. Hum Mutat. 2007;28:781-9.
17. van Wijk E, Pennings RJ, te Brinke H, Claassen A, Yntema HG, Hoefsloot LH, et al. Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II. Am J Hum Genet. 2004;74:738-44.
18. Adato A, Weston MD, Berry A, Kimberling WJ, Bonne-Tamir A. Three novel mutations and twelve polymorphisms identified in the USH2A gene in Israeli USH2 families. Hum Mutat. 2000;15:388.
19. Nelson MR, Marnellos G, Kammerer S, Hoyal CR, Shi MM, Cantor CR, et al. Large-scale validation of single nucleotide polymorphisms in gene regions. Genome Res. 2004;14:1664-8.
20. Spandau UH, Rohrschneider K. Prevalence and geographical distribution of Usher syndrome in Germany. Graefes Arch Clin Exp Ophthalmol. 2002;240:495-8.
21. Bernal S, Ayuso C, Antinolo G, Gimenez A, Borrego S, Trujillo MJ, et al. Mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa: high prevalence and phenotypic variation. J Med Genet. 2003;40:e8.
22. Dreyer B, Tranebjaerg L, Rosenberg T, Weston MD, Kimberling WJ, Nilssen O. Identification of novel USH2A mutations: Implications for the structure of USH2A protein. Eur J Hum Genet. 2000;8:500-6.
23. Leroy BP, Aragón-Martín JA, Weston MD, Bessant DA, Willis C, Webster AR, et al. Spectrum of mutations in USH2A in British patients with Usher syndrome type II. Exp Eye Res. 2001;72:503-9.
24. Beneyto MM, Cuevas JM, Millan JM, Espinos C, Mateu E, González-Cabo P, et al. Prevalence of 2314delG mutation in Spanish patients with Usher syndrome type II (USH2). Ophthalmic Genet. 2000;21:123-8.
25. Maubaret C, Griffoin JM, Arnaud B, Hamel C. Novel mutations in MYO7A and USH2A in Usher syndrome. Ophthalmic Genet. 2005;26:25-9.
26. Dai H, Zhang X, Zhao X, Deng T, Dong B, Wang J, et al. Identification of five novel mutations in the long isoform of the USH2A gene in Chinese families with Usher syndrome type II. Mol Vis. 2008;14:2067-75.
27. McGee TL, Seyedahmadi BJ, Sweeney MO, Dryja TP, Berson EL. Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa. J Med Genet. 2010;47:499-506.
28. Rohlin A, Wernersson J, Engwall Y, Wiklund L, Bjork J, Nordling M. Parallel sequencing used in detection of mosaic mutations: Comparison with four diagnostic DNA screening techniques. Hum Mutat. 2009;30:1012-20.
29. Aller E, Larrieu L, Jaijo T, Baux D, Espinos C, González-Candelas F, et al. The USH2A c.2299delG mutation: Dating its common origin in a Southern European population. Eur J Hum Genet. 2010;18:788-93.
30. Nakanishi H, Ohtsubo M, Iwasaki S, Hotta Y, Mizuta K, Mineta H, et al. Identification of 11 novel mutations in USH2A among Japanese patients with Usher syndrome type 2. Clin Genet. 2009;76:383-91.
31. Dreyer B, Brox V, Tranebjaerg L, Rosenberg T, Sadeghi AM, Moller C, et al. Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II. Hum Mutat. 2008;29:451.
32. Jaijo T, Aller E, García-García G, Aparisi MJ, Bernal S, Ávila-Fernández A, et al. Microarray-based mutation analysis of 183 Spanish families with Usher syndrome. Invest Ophthalmol Vis Sci. 2010;51:1311-7.
How to Cite
1.
López G, Gelvez NY, Tamayo M. Mutational frequencies in usherin (USH2A gene) in 26 Colombian individuals with Usher syndrome type II. biomedica [Internet]. 2011 Apr. 16 [cited 2024 May 12];31(1):82-90. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/338
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