Phenotypic variability of RP1-related inherited retinal dystrophy associated with the c.5797 C > T (p.Arg1933*) variant in the Japanese population.
Humans
Male
Female
Middle Aged
Adult
Phenotype
Japan
Eye Proteins
/ genetics
Retinal Dystrophies
/ genetics
Retrospective Studies
Electroretinography
Genetic Association Studies
Aged
Adolescent
Young Adult
Retinitis Pigmentosa
/ genetics
Mutation
Codon, Nonsense
Child
Asian People
/ genetics
Cone-Rod Dystrophies
/ genetics
East Asian People
Microtubule-Associated Proteins
Cone-rod dystrophy
Macular dystrophy
Retinitis pigmentosa
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 Oct 2024
27 Oct 2024
Historique:
received:
07
08
2024
accepted:
22
10
2024
medline:
28
10
2024
pubmed:
28
10
2024
entrez:
28
10
2024
Statut:
epublish
Résumé
The phenotypes of RP1-related inherited retinal dystrophies (RP1-IRD), causing autosomal dominant (AD) and autosomal recessive (AR) diseases, vary depending on specific RP1 variants. A common nonsense mutation near the C-terminus, c.5797 C > T (p.Arg1933*), is associated with RP1-IRD, but the exact role of this mutation in genotype-phenotype correlation remains unclear. In this study, we retrospectively analyzed patients with RP1-IRD (N = 42) from a single center in Japan. AR RP1-IRD patients with the c.5797 C > T mutation (N = 14) mostly displayed macular dystrophy but rarely retinitis pigmentosa or cone-rod dystrophy. Conversely, AR RP1-IRD patients without the c.5797 C > T mutation, including those with other pathogenic RP1 variants, were mostly diagnosed with severe retinitis pigmentosa. Full-field electroretinograms were significantly better in patients homozygous or compound heterozygous for the c.5797 C > T mutation than in those without this mutation, corresponding to their milder phenotypes. Clinical tests also revealed a slower onset of age and a better mean deviation value with the static visual field in AR RP1-IRD patients with the c.5797 C > T mutation compared to those without. Therefore, the presence of c.5797 C > T may partly account for the phenotypic variety of RP1-IRD and may yield milder phenotypes. These findings may be useful for predicting the prognosis of RP1-IRD patients.
Identifiants
pubmed: 39463394
doi: 10.1038/s41598-024-77441-3
pii: 10.1038/s41598-024-77441-3
doi:
Substances chimiques
RP1 protein, human
0
Eye Proteins
0
Codon, Nonsense
0
Microtubule-Associated Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25669Subventions
Organisme : the Japan Society for the Promotion of Science (JSPS) KAKENHI
ID : 23K15929
Organisme : the Japan Society for the Promotion of Science (JSPS) KAKENHI
ID : 23H03059
Organisme : Japan Agency for Medical Research and Development
ID : 23ym0126071h0002
Informations de copyright
© 2024. The Author(s).
Références
Pagon, R. A. Retinitis pigmentosa. Surv. Ophthalmol. 33, 137–177 (1988).
doi: 10.1016/0039-6257(88)90085-9
pubmed: 3068820
Verbakel, S. K. et al. Non-syndromic retinitis pigmentosa. Prog. Retin. Eye Res. 66, 157–186 (2018).
doi: 10.1016/j.preteyeres.2018.03.005
pubmed: 29597005
Hartong, D. T., Berson, E. L. & Dryja, T. P. Retinitis pigmentosa. Lancet 368, 1795–1809 (2006).
doi: 10.1016/S0140-6736(06)69740-7
pubmed: 17113430
Ran, X. et al. ‘RetinoGenetics’: A comprehensive mutation database for genes related to inherited retinal degeneration. Database (Oxford) 2014, bau047 (2014).
Pierce, E. A. et al. Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa. Nat. Genet. 22, 248–254 (1999).
doi: 10.1038/10305
pubmed: 10391211
Liu, Q. et al. Identification and subcellular localization of the RP1 protein in human and mouse photoreceptors. Invest. Ophthalmol. Vis. Sci. 43, 22–32 (2002).
pubmed: 11773008
Sullivan, L. S. et al. Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa. Nat. Genet. 22, 255–259 (1999).
doi: 10.1038/10314
pubmed: 10391212
pmcid: 2582380
Khaliq, S. et al. Novel association of RP1 gene mutations with autosomal recessive retinitis pigmentosa. J. Med. Genet. 42, 436–438 (2005).
doi: 10.1136/jmg.2004.024281
pubmed: 15863674
pmcid: 1736063
Ferré, C., Espino, A., Cruzado, J. M. & Carratalá, J. Severe neurologic toxicity from oral acyclovir. Med. Clin. (Barc). 98, 679 (1992).
pubmed: 1598021
Avila-Fernandez, A. et al. Identification of an RP1 prevalent founder mutation and related phenotype in Spanish patients with early-onset autosomal recessive retinitis. Ophthalmology. 119, 2616–2621 (2012).
doi: 10.1016/j.ophtha.2012.06.033
pubmed: 22917891
Kurata, K., Hosono, K. & Hotta, Y. Clinical and genetic findings of a Japanese patient with RP1-related autosomal recessive retinitis pigmentosa. Doc. Ophthalmol. 137, 47–56 (2018).
doi: 10.1007/s10633-018-9649-7
pubmed: 30027431
Verbakel, S. K. et al. Macular dystrophy and cone-rod dystrophy caused by mutations in the RP1 gene: extending the rp1 disease spectrum. Invest. Ophthalmol. Vis. Sci. 60, 1192–1203 (2019).
doi: 10.1167/iovs.18-26084
pubmed: 30913292
Riera, M. et al. Expanding the retinal phenotype of RP1: from retinitis pigmentosa to a novel and singular macular dystrophy. Br. J. Ophthalmol. 104, 173–181 (2020).
doi: 10.1136/bjophthalmol-2018-313672
pubmed: 31079053
Nishiguchi, K. M. et al. Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and NEK2 as a new disease gene. Proc. Natl. Acad. Sci. USA. 110, 16139–16144 (2013).
Nishiguchi, K. M. et al. A founder Alu insertion in RP1 gene in Japanese patients with retinitis pigmentosa. Jpn J. Ophthalmol. 64, 346–350 (2020).
doi: 10.1007/s10384-020-00732-5
pubmed: 32193659
Oishi, M. et al. Comprehensive molecular diagnosis of a large cohort of Japanese retinitis pigmentosa and Usher syndrome patients by next-generation sequencing. Invest. Ophthalmol. Vis. Sci. 55, 7369–7375 (2014).
doi: 10.1167/iovs.14-15458
pubmed: 25324289
Maeda, A. et al. Development of a molecular diagnostic test for retinitis pigmentosa in the Japanese population. Jpn J. Ophthalmol. 62, 451–457 (2018).
doi: 10.1007/s10384-018-0601-x
pubmed: 29785639
Kawamura, M. et al. Novel 2336-2337delCT mutation in RP1 gene in a Japanese family with autosomal dominant retinitis pigmentosa. Am. J. Ophthalmol. 137, 1137–1139 (2004).
doi: 10.1016/j.ajo.2003.12.037
pubmed: 15183808
Nikopoulos, K. et al. A frequent variant in the Japanese population determines quasi-mendelian inheritance of rare retinal ciliopathy. Nat. Commun. 10, 2884 (2019).
doi: 10.1038/s41467-019-10746-4
pubmed: 31253780
pmcid: 6599023
Wang, P. et al. An ophthalmic targeted exome sequencing panel as a powerful tool to identify causative mutations in patients suspected of hereditary eye diseases. Transl Vis. Sci. Technol. 8, 21 (2019).
doi: 10.1167/tvst.8.2.21
pubmed: 31788350
pmcid: 6871542
Neveling, K. et al. Next-generation genetic testing for retinitis pigmentosa. Hum. Mutat. 33, 963–972 (2012).
doi: 10.1002/humu.22045
pubmed: 22334370
pmcid: 3490376
Alfano, G. et al. EYS is a protein associated with the ciliary axoneme in rods and cones. PLoS One. 11, e0166397 (2016).
doi: 10.1371/journal.pone.0166397
pubmed: 27846257
pmcid: 5112921
Mizobuchi, K. et al. Genotype-phenotype correlations in RP1-associated retinal dystrophies: a multi-center cohort study in Japan. J. Clin. Med. 10, 2265 (2021).
doi: 10.3390/jcm10112265
pubmed: 34073704
pmcid: 8197273
Lafont, E. et al. Patients with retinitis pigmentosa due to RP1 mutations show greater severity in recessive than in dominant cases. J. Clin. Exp. Ophthalmol. 2, 12 (2012).
Ueno, S. et al. Clinical characteristics and high resolution retinal imaging of retinitis pigmentosa caused by RP1 gene variants. Jpn J. Ophthalmol. 64, 485–496 (2020).
doi: 10.1007/s10384-020-00752-1
pubmed: 32627106
Koyanagi, Y. et al. Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients. J. Med. Genet. 56, 662–670 (2019).
doi: 10.1136/jmedgenet-2018-105691
pubmed: 31213501
Fujinami, K., Nishiguchi, K. M., Oishi, A., Akiyama, M. & Ikeda, Y. Specification of variant interpretation guidelines for inherited retinal dystrophy in Japan. Jpn J. Ophthalmol. 68, 389–399 (2024).
doi: 10.1007/s10384-024-01063-5
pubmed: 39078460
Goto, K. et al. Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases. J. Med. Genet. 61, 613–620 (2023).
Won, D. et al. In silico identification of a common mobile element insertion in exon 4 of RP1. Sci. Rep. 11, 13381 (2021).
doi: 10.1038/s41598-021-92834-4
pubmed: 34183725
pmcid: 8238996
Nanda, A., McClements, M. E., Clouston, P., Shanks, M. E. & MacLaren, R. E. The location of exon 4 mutations in RP1 raises challenges for genetic counseling and gene therapy. Am. J. Ophthalmol. 202, 23–29 (2019).
doi: 10.1016/j.ajo.2019.01.027
pubmed: 30731082
Grover, S., Fishman, G. A., Alexander, K. R., Anderson, R. J. & Derlacki, D. J. Visual acuity impairment in patients with retinitis pigmentosa. Ophthalmology. 103, 1593–1600 (1996).
doi: 10.1016/S0161-6420(96)30458-2
pubmed: 8874431
Kominami, T. et al. Associations between outer retinal structures and focal macular electroretinograms in patients with retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 58, 5122–5128 (2017).
doi: 10.1167/iovs.17-22040
pubmed: 28986597