Advertisement

Rhodopsin gene mutation analysis in Iranian patients with autosomal dominant retinitis pigmentosa

  • Danial Roshandel
  • Maryam Rafati
  • Sara Khorami
  • Nima Novin Baheran
  • Setareh Jalali
  • Razieh Tabatabaie
  • Safura Rezai
  • Hamid Ahmadieh
  • Saeed Reza GhaffariEmail author
Original Paper

Abstract

Purpose

Retinitis pigmentosa (RP) is the most common hereditary retinal degeneration and an important cause of visual disability worldwide. Rhodopsin gene is one of the most important genes implicated in autosomal dominant RP (ADRP). In this study, we investigated rhodopsin gene mutations in Iranian patients with ADRP.

Methods

Twenty-one patients from 21 unrelated families with a total of 51 affected members were enrolled in this study. After complete history taking, ophthalmic examination and genetic counseling, peripheral blood samples were obtained. Following genomic DNA extraction, all five exons and intron–exon boundaries of RHO gene were sequenced using Sanger method. Interpretation of detected variants was carried out using appropriate databases and bioinformatic tools. Novel variants were screened in 150 unrelated healthy subjects.

Results

Results of direct sequencing revealed that five of 21 patients (23.8%) had mutation in the rhodopsin gene. Two of them had previously identified p.P347L mutation, and three had novel variants including p.L95P, p.R177K and p.N310K. None of these novel variants were detected in healthy controls. The p.L95P variant was associated with predominantly inferior retinal involvement.

Conclusions

Our study showed that mutations of the rhodopsin gene are relatively frequent in Iranian patients with ADRP and could be considered in further researches in the future. The novel p.L95P variant may be associated with a specific pattern of retinal degeneration in this population.

Keywords

Retinitis pigmentosa Rhodopsin Mutation Genotype–phenotype correlation 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Berson EL (1993) Retinitis pigmentosa. The Friedenwald lecture. Investig Ophthalmol Vis Sci 34:1659–1676Google Scholar
  2. 2.
    Cideciyan AV, Hood DC, Huang Y et al (1998) Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man. Proc Natl Acad Sci USA 95:7103–7108CrossRefGoogle Scholar
  3. 3.
    Ando Y, Ohmori M, Ohtake H et al (2007) Mutation screening and haplotype analysis of the rhodopsin gene locus in Japanese patients with retinitis pigmentosa. Mol Vis 13:1038–1044Google Scholar
  4. 4.
    Dryja TP, Hahn LB, Cowley GS et al (1991) Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa. Proc Natl Acad Sci USA 88:9370–9374CrossRefGoogle Scholar
  5. 5.
    Sung C-H, Davenport CM, Hennessey JC et al (1991) Rhodopsin mutations in autosomal dominant retinitis pigmentosa. Proc Natl Acad Sci USA 88:6481–6485CrossRefGoogle Scholar
  6. 6.
    Blanco-Kelly F, García-Hoyos M, Cortón M et al (2012) Genotyping microarray: mutation screening in Spanish families with autosomal dominant retinitis pigmentosa. Mol Vis 18:1478–1483Google Scholar
  7. 7.
    Sullivan LS, Bowne SJ, Birch DG et al (2006) Prevalence of disease-causing mutations in families with autosomal dominant retinitis pigmentosa: a screen of known genes in 200 families. Investig Ohthalmol Vis Sci 47:3052–3064CrossRefGoogle Scholar
  8. 8.
    Jose FS, Blanco-Kelly F, Corton M et al (2015) Prevalence of rhodopsin mutations in autosomal dominant retinitis pigmentosa in Spain: clinical and analytical review in 200 families. Acta Ophthalmol 93:e38–e44CrossRefGoogle Scholar
  9. 9.
    Dryja TP, McGee TL, Reichel E et al (1990) A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343:364–366CrossRefGoogle Scholar
  10. 10.
    Farrar G, Kenna P, Redmond R et al (1990) Autosomal dominant retinitis pigmentosa: absence of the rhodopsin proline—histidine substitution (codon 23) in pedigrees from Europe. Am J Hum Genet 47:941–945Google Scholar
  11. 11.
    Sohocki MM, Daiger SP, Bowne SJ et al (2001) Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies. Hum Mutat 17:42–51CrossRefGoogle Scholar
  12. 12.
    Mendes HF, van der Spuy J, Chapple JP et al (2005) Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy. Trends Mol Med 11:177–185CrossRefGoogle Scholar
  13. 13.
    Naash ML, Peachey NS, Li Z-Y et al (1996) Light-induced acceleration of photoreceptor degeneration in transgenic mice expressing mutant rhodopsin. Investig Ophthalmol Vis Sci 37:775–782Google Scholar
  14. 14.
    Aleman TS, Cideciyan AV, Sumaroka A et al (2008) Retinal laminar architecture in human retinitis pigmentosa caused by rhodopsin gene mutations. Investig Ophthalmol Vis Sci 49:1580–1590CrossRefGoogle Scholar
  15. 15.
    Audo I, Manes G, Mohand-Saïd S et al (2010) Spectrum of rhodopsin mutations in French autosomal dominant rod-cone dystrophy patients. Investig Ophthalmol Vis Sci 51:3687–3700CrossRefGoogle Scholar
  16. 16.
    Ziviello C, Simonelli F, Testa F et al (2005) Molecular genetics of autosomal dominant retinitis pigmentosa (ADRP): a comprehensive study of 43 Italian families. J Med Genet 42:e47CrossRefGoogle Scholar
  17. 17.
    Inglehearn CF, Tarttelin EE, Plant C et al (1998) A linkage survey of 20 dominant retinitis pigmentosa families: frequencies of the nine known loci and evidence for further heterogeneity. J Med Genet 35:1–5CrossRefGoogle Scholar
  18. 18.
    Xu Y, Guan L, Shen T et al (2014) Mutations of 60 known causative genes in 157 families with retinitis pigmentosa based on exome sequencing. Hum Genet 133:1255–1271CrossRefGoogle Scholar
  19. 19.
    Kim KJ, Kim C, Bok J et al (2011) Spectrum of rhodopsin mutations in Korean patients with retinitis pigmentosa. Mol Vis 17:844–853Google Scholar
  20. 20.
    Hugosson T, Friedman JS, Ponjavic V et al (2010) Phenotype associated with mutation in the recently identified autosomal dominant retinitis pigmentosa KLHL7 gene. Arch Ophthalmol 128:772–778CrossRefGoogle Scholar
  21. 21.
    Richards CS, Bale S, Bellissimo DB et al (2008) ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet Med 10:294–300CrossRefGoogle Scholar
  22. 22.
    Paskowitz DM, LaVail MM, Duncan JL (2006) Light and inherited retinal degeneration. Br J Ophthalmol 90:1060–1066CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Danial Roshandel
    • 1
  • Maryam Rafati
    • 2
    • 3
    • 4
  • Sara Khorami
    • 2
  • Nima Novin Baheran
    • 4
  • Setareh Jalali
    • 1
  • Razieh Tabatabaie
    • 4
  • Safura Rezai
    • 4
  • Hamid Ahmadieh
    • 5
  • Saeed Reza Ghaffari
    • 2
    • 3
    • 4
    Email author
  1. 1.Ocular Tissue Engineering Research CenterShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Reproductive Biotechnology Research Center, Avicenna Research InstituteACECRTehranIran
  3. 3.Fetal Health Research CenterHope Generation FoundationTehranIran
  4. 4.Gene ClinicTehranIran
  5. 5.Ophthalmic Research CenterShahid Beheshti University of Medical SciencesTehranIran

Personalised recommendations