Abstract
Retinal degenerations represent a heterogeneous group of disorders affecting the function of the retina. The frequency of retinitis pigmentosa (RP) is 1/3500 worldwide, however, in northern Sweden it is 1/2000 due to limited migration and a ‘founder’ effect. In this study we identified genetic mechanisms underlying autosomal dominant and recessive RP present in northern Sweden. Several novel mutations unique for this region were found. In an autosomal recessive form of RP, Bothnia dystrophy caused by mutations in the RLBP1 gene, bi-allelic mutations R234W, M226K and compound heterozygosity, M226K+R234W was detected.
In dominant form of RP mapped to 19q13.42 a 59 kb genomic deletion including the PRPF31 and three other genes was found.
These data provide additional information on the molecular mechanisms of RP evolvement and in the future might be useful in development of therapeutic strategies. Identification of the disease-causing mutations allowed introducing molecular genetic testing of the patients and their families into the clinical practice.
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References
Abu-Safieh L, Vithana EN, Mantel I et al (2006) A large deletion in the adRP gene PRPF31: evidence that haploinsufficiency is the cause of disease. Mol Vis 12:384–388
Al-Maghtheh M, Inglehearn CF, Keen TJ et al (1994) Identification of a sixth locus for autosomal dominant retinitis pigmentosa on chromosome 19. Hum Mol Genet 3:351–354
Burstedt MSI, Forsman-Semb K, Golovleva I et al (2001) Ocular phenotype of Bothnia dystrophy, an autosomal recessive retinitis pigmentosa associated with an P.R234Wmutation in the RLBP1 gene. Arch Ophthalmol 119:260–267
Burstedt MSI, Sandgren O, Holmgren G et al (1999) Bothnia dystrophy caused by mutation in the cellular retinaldehyde-binding protein gene (RLBP1) on chromosome 15q26. Invest Ophthalmol Visl Sci 40:995–1000
Humbert G, Delettre C, Senechal A et al (2006) Homozygous deletion related to Alu repeats in RLBP1 causes retinitis punctata albescens. Invest Ophthalmol Vis Sci 47:4719–4724
Köhn L, Kadzhaev K, Burstedt MSI et al (2007) Mutation in PYK2-binding domain of the PITPNM3 causes autosomal dominant cone dystrophy (CORD5). Eur J Hum Genet 15:664–671
Makarova OV, Makarov EM, Liu S et al (2002) Protein 61 K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6*U5 tri-snRNP formation and pre-mRNA splicing. EMBO J 21:1148–1157
Martinez-Gimeno M, Gamundi MJ, Hernan I et al (2003) Mutations in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31 in Spanish families with autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 44:2171–2177
Pastinen T, Kurg A, Metspalu A et al (1997) Minisequencing: a specific tool for DNA analysis and diagnostics on oligonucleotide arrays. Genome Res 7:606–614
Rebello G, Ramesar R, Vorster A et al (2004) Apoptosis-inducing signal sequence mutation in carbonic anhydrase IV identified in patients with the RP17 form of retinitis pigmentosa. Proc Natl Acad Sci USA 101:6617–6622
Sato H, Wada Y, Itabashi T, Nakamura M, Kawamura M, Tamai M (2005) Mutations in the pre-mRNA splicing gene, PRPF31, in Japanese families with autosomal dominant retinitis pigmentosa. Am J Ophthalmol 140:537–540
Sullivan LS, Bowne SJ, Seaman CR et al (2006) Genomic rearrangements of the PRPF31 gene account for 2.5% of autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 47:4579–4588
Vithana EN, Abu-Safieh L, Allen MJ et al (2001) A human homolog of yeast pre-mRNA splicing gene, PRPF31, underlies autosomal dominant retinitis pigmentosa on chromosome 19q13.4 (RP11). Mol Cell 8:375–381
Yang Z, Alvarez BV, Chakarova C et al (2005) Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration. Hum Mol Genet 14:255–265
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Golovleva, I., Köhn, L., Burstedt, M., Daiger, S., Sandgren, O. (2010). Mutation Spectra in Autosomal Dominant and Recessive Retinitis Pigmentosa in Northern Sweden. In: Anderson, R., Hollyfield, J., LaVail, M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 664. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1399-9_29
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DOI: https://doi.org/10.1007/978-1-4419-1399-9_29
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