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Documenta Ophthalmologica

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01-08-2018 | Clinical Case Report

Clinical and genetic findings of a Japanese patient with RP1-related autosomal recessive retinitis pigmentosa

Authors: Kentaro Kurata, Katsuhiro Hosono, Yoshihiro Hotta

Published in: Documenta Ophthalmologica | Issue 1/2018

Abstract

Purpose

This study reports the ophthalmic and genetic findings of a Japanese patient with autosomal recessive retinitis pigmentosa (arRP) caused by retinitis pigmentosa 1 (RP1) mutations.

Patient and methods

The 34-year-old female patient and her unaffected parents underwent comprehensive ophthalmic examinations, including visual acuity measurements, perimetry, electroretinography (ERG), and optical coherence tomography. Fundus autofluorescence was also evaluated in the patient. To identify potential pathogenic variants, 111 inherited eye disease genes were examined by targeted next-generation sequencing.

Results

The patient had night blindness from the first decade of her life. Fundus examination revealed typical RP findings with additional macular degeneration. Her visual field and acuity were severely affected, and ERG scans showed undetectable responses. Bioinformatics analysis revealed two heterozygous potentially pathogenic variants in RP1 in the patient, one of which is novel. Co-segregation analysis in the unaffected parents confirmed that the two variants were in trans. The parents were both carriers of one RP1 variant but did not show any visual symptoms. Therefore, the identified compound heterozygous variants were proposed as the probable arRP-causing mutations in the family.

Conclusion

This is the first description of a Japanese patient with arRP caused by RP1 mutations. Additional data are necessary to more accurately determine the clinical course and mutation spectrum in patients with RP1-related arRP.

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Chizzolini M, Galan A, Milan E, Sebastiani A, Costagliola C, Parmeggiani F (2011) Good epidemiologic practice in retinitis pigmentosa: from phenotyping to biobanking. Curr Genom 12:260–266. https://doi.org/10.2174/138920211795860071 CrossRef

Daiger SD, Sullivan LS, Bowne SJ. The Retinal Information Network. The University of Texas Health Science Center. http://www.sph.uth.tmc.edu/Retnet/. Accessed 11 Jan 2017

Ran X, Cai WJ, Huang XF, Liu Q, Lu F, Qu J, Wu J, Jin ZB (2014) “RetinoGenetics”: a comprehensive mutation database for genes related to inherited retinal degeneration. Database. https://doi.org/10.1093/database/bau047 PubMedCrossRefPubMedCentral

Pierce EA, Quinn T, Meehan T, McGee TL, Berson EL, Dryja TP (1999) Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa. Nat Genet 22:248–254. https://doi.org/10.1038/10305 CrossRefPubMed

Hartong DT, Berson EL, Dryja TP (2006) Retinitis pigmentosa. Lancet 368:1795–1809. https://doi.org/10.1016/S0140-6736(06)69740-7 CrossRefPubMed

Liu Q, Zhou J, Daiger SP, Farber DB, Heckenlively JR, Smith JE, Sullivan LS, Zuo J, Milam AH, Pierce EA (2002) Identification and subcellular localization of the RP1 protein in human and mouse photoreceptors. Invest Ophthalmol Vis Sci 43:22–32PubMedPubMedCentral

Dietrich K, Jacobi FK, Tippmann S, Schmid R, Zrenner E, Wissinger B, Apfelstedt-Sylla E (2002) A novel mutation of the RP1 gene (Lys778ter) associated with autosomal dominant retinitis pigmentosa. Br J Ophthalmol 86:328–332. https://doi.org/10.1136/bjo.86.3.328 CrossRefPubMedPubMedCentral

Jacobson SG, Cideciyan AV, Iannaccone A, Weleber RG, Fishman GA, Maguire AM, Affatigato LM, Bennett J, Pierce EA, Danciger M, Farber DB, Stone EM (2000) Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 41:1898–1908PubMed

Bowne SJ, Daiger SP, Hims MM, Sohocki MM, Malone KA, McKie AB, Heckenlively JR, Birch DG, Inglehearn CF, Bhattacharya SS, Bird A, Sullivan LS (1999) Mutations in the RP1 gene causing autosomal dominant retinitis pigmentosa. Hum Mol Genet 8:2121–2128. https://doi.org/10.1093/hmg/8.11.2121 CrossRefPubMedPubMedCentral

10.

Berson EL, Grimsby JL, Adams SM, McGee TL, Sweklo E, Pierce EA, Sandberg MA, Dryja TP (2001) Clinical features and mutations in patients with dominant retinitis pigmentosa-1 (RP1). Invest Ophthalmol Vis Sci 42:2217–2224PubMed

11.

Schwartz SB, Aleman TS, Cideciyan AV, Swaroop A, Jacobson SG, Stone EM (2003) De novo mutation in the RP1 gene (Arg677ter) associated with retinitis pigmentosa. Invest Ophthalmol Vis Sci 44:3593–3597CrossRefPubMed

12.

Kawamura M, Wada Y, Noda Y, Itabashi T, Ogawa S, Sato H, Tanaka K, Ishibashi T, Tamai M (2004) Novel 2336-2337delCT mutation in RP1 gene in a Japanese family with autosomal dominant retinitis pigmentosa. Am J Ophthalmol 137:1137–1139. https://doi.org/10.1016/j.ajo.2003.12.037 CrossRefPubMed

13.

El Shamieh S, Boulanger-Scemama E, Lancelot ME, Antonio A, Démontant V, Condroyer C, Letexier M, Saraiva JP, Mohand-Saïd S, Sahel JA, Audo I, Zeitz C (2015) Targeted next generation sequencing identifies novel mutations in RP1 as a relatively common cause of autosomal recessive rod-cone dystrophy. Biomed Res Int 2015:485624. https://doi.org/10.1155/2015/485624 CrossRefPubMedPubMedCentral

14.

Chen LJ, Lai TY, Tam PO, Chiang SW, Zhang X, Lam S, Lai RY, Lam DS, Pang CP (2010) Compound heterozygosity of two novel truncation mutations in RP1 causing autosomal recessive retinitis pigmentosa. Invest Ophthalmol Vis Sci 51:2236–2242. https://doi.org/10.1167/iovs.09-4437 CrossRefPubMed

15.

Kabir F, Ullah I, Ali S, Gottsch AD, Naeem MA, Assir MZ, Khan SN, Akram J, Riazuddin S, Ayyagari R, Hejtmancik JF, Riazuddin SA (2016) Loss of function mutations in RP1 are responsible for retinitis pigmentosa in consanguineous familial cases. Mol Vis 22:610–625PubMedPubMedCentral

16.

Siemiatkowska AM, Astuti GD, Arimadyo K, den Hollander AI, Faradz SM, Cremers FP, Collin RW (2012) Identification of a novel nonsense mutation in RP1 that causes autosomal recessive retinitis pigmentosa in an Indonesian family. Mol Vis 18:2411–2419PubMedPubMedCentral

17.

Avila-Fernandez A, Corton M, Nishiguchi KM, Muñoz-Sanz N, Benavides-Mori B, Blanco-Kelly F, Riveiro-Alvarez R, Garcia-Sandoval B, Rivolta C, Ayuso C (2012) Identification of an RP1 prevalent founder mutation and related phenotype in Spanish patients with early-onset autosomal recessive retinitis. Ophthalmology 119:2616–2621. https://doi.org/10.1016/j.ophtha.2012.06.033 CrossRefPubMed

18.

Al-Rashed M, Abu Safieh L, Alkuraya H, Aldahmesh MA, Alzahrani J, Diya M, Hashem M, Hardcastle AJ, Al-Hazzaa SA, Alkuraya FS (2012) RP1 and retinitis pigmentosa: report of novel mutations and insight into mutational mechanism. Br J Ophthalmol 96:1018–1022. https://doi.org/10.1136/bjophthalmol-2011-301134 CrossRefPubMed

19.

Riazuddin SA, Zulfiqar F, Zhang Q, Sergeev YV, Qazi ZA, Husnain T, Caruso R, Riazuddin S, Sieving PA, Hejtmancik JF (2005) Autosomal recessive retinitis pigmentosa is associated with mutations in RP1 in three consanguineous Pakistani families. Invest Ophthalmol Vis Sci 46:2264–2270. https://doi.org/10.1167/iovs.04-1280 CrossRefPubMed

20.

Singh HP, Jalali S, Narayanan R, Kannabiran C (2009) Genetic analysis of Indian families with autosomal recessive retinitis pigmentosa by homozygosity screening. Invest Ophthalmol Vis Sci 50:4065–4071. https://doi.org/10.1167/iovs.09-3479 CrossRefPubMedPubMedCentral

21.

McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R, Bach M (2015) ISCEV Standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130:1–12. https://doi.org/10.1007/s10633-014-9473-7 CrossRefPubMed

22.

The Human Gene Mutation Database. Institute of Medical Genetics in Cardiff. http://www.hgmd.cf.ac.uk/ac/index.php. Accessed 11 Jan 2017

23.

Hosono K, Harada Y, Kurata K, Hikoya A, Sato M, Minoshima S, Hotta Y (2015) Novel GUCY2D gene mutations in Japanese male twins with Leber congenital amaurosis. J Ophthalmol 2015:693468. https://doi.org/10.1155/2015/693468 CrossRefPubMedPubMedCentral

24.

The 1000 Genomes Project data. In: The 1000 Genomes Project Consortium. http://www.1000genomes.org/. Accessed 11 Jan 2017

25.

ExAC database. In: The Exome Aggregation Consortium. http://exac.broadinstitute.org/. Accessed 11 Jan 2017

26.

Higasa K, Miyake N, Yoshimura J. Human genetic variation database. Kyoto University, Japan. http://www.genome.med.kyoto-u.ac.jp/SnpDB/. Accessed 11 Jan 2017

27.

Integrative Japanese Genome Variation Database. Tohoku University, Japan. https://ijgvd.megabank.tohoku.ac.jp/. Accessed 11 Jan 2017

28.

Hosono K, Ishigami C, Takahashi M, Park DH, Hirami Y, Nakanishi H, Ueno S, Yokoi T, Hikoya A, Fujita T, Zhao Y, Nishina S, Shin JP, Kim IT, Yamamoto S, Azuma N, Terasaki H, Sato M, Kondo M, Minoshima S, Hotta Y (2012) Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population. PLoS ONE 7:e31036. https://doi.org/10.1371/journal.pone.0031036 CrossRefPubMedPubMedCentral

29.

Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-Juan A, Hull S, Megy K, Grozeva D, Dewhurst E, Malka S, Plagnol V, Penkett C, Stirrups K, Rizzo R, Wright G, Josifova D, Bitner-Glindzicz M, Scott RH, Clement E, Allen L, Armstrong R, Brady AF, Carmichael J, Chitre M, Henderson RHH, Hurst J, MacLaren RE, Murphy E, Paterson J, Rosser E, Thompson DA, Wakeling E, Ouwehand WH, Michaelides M, Moore AT, Webster AR, Raymond FL, NIHR-BioResource Rare Diseases Consortium (2017) Comprehensive rare variant analysis via whole-genome sequencing to determine the molecular pathology of inherited retinal disease. Am J Hum Genet 100:75–90. https://doi.org/10.1016/j.ajhg.2016.12.003 CrossRefPubMed

30.

Payne A, Vithana E, Khaliq S, Hameed A, Deller J, Abu-Safieh L, Kermani S, Leroy BP, Mehdi SQ, Moore AT, Bird AC, Bhattacharya SS (2000) RP1 protein truncating mutations predominate at the RP1 adRP locus. Invest Ophthalmol Vis Sci 41:4069–4073PubMed

31.

Neveling K, Collin RW, Gilissen C, van Huet RA, Visser L, Kwint MP, Gijsen SJ, Zonneveld MN, Wieskamp N, de Ligt J, Siemiatkowska AM, Hoefsloot LH, Buckley MF, Kellner U, Branham KE, den Hollander AI, Hoischen A, Hoyng C, Klevering BJ, van den Born LI, Veltman JA, Cremers FP, Scheffer H (2012) Next-generation genetic testing for retinitis pigmentosa. Hum Mutat 33:963–972CrossRefPubMedPubMedCentral

32.

Liu X, Xiao J, Huang H, Guan L, Zhao K, Xu Q, Zhang X, Pan X, Gu S, Chen Y, Zhang J, Shen Y, Jiang H, Gao X, Kang X, Sheng X, Chen X, Zhao C (2015) Molecular genetic testing in clinical diagnostic assessments that demonstrate correlations in patients with autosomal recessive inherited retinal dystrophy. JAMA Ophthalmol 133:427–436. https://doi.org/10.1001/jamaophthalmol.2014.5831 CrossRefPubMed

33.

Méndez-Vidal C, Bravo-Gil N, González-Del Pozo M, Vela-Boza A, Dopazo J, Borrego S, Antiñolo G (2014) Novel RP1 mutations and a recurrent BBS1 variant explain the co-existence of two distinct retinal phenotypes in the same pedigree. BMC Genet 15:143. https://doi.org/10.1186/s12863-014-0143-2 CrossRefPubMedPubMedCentral

34.

Audo I, Mohand-Saïd S, Dhaenens CM, Germain A, Orhan E, Antonio A, Hamel C, Sahel JA, Bhattacharya SS, Zeitz C (2012) RP1 and autosomal dominant rod-cone dystrophy: novel mutations, a review of published variants, and genotype-phenotype correlation. Hum Mutat 33:73–80. https://doi.org/10.1002/humu.21640 CrossRefPubMed

35.

Huang XF, Huang F, Wu KC, Wu J, Chen J, Pang CP, Lu F, Qu J, Jin ZB (2015) Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing. Genet Med 17:271–278CrossRefPubMed

Title: Clinical and genetic findings of a Japanese patient with RP1-related autosomal recessive retinitis pigmentosa
Authors: Kentaro Kurata
Katsuhiro Hosono
Yoshihiro Hotta
Publication date: 01-08-2018
Publisher: Springer Berlin Heidelberg
Published in: Documenta Ophthalmologica / Issue 1/2018
Print ISSN: 0012-4486
Electronic ISSN: 1573-2622
DOI: https://doi.org/10.1007/s10633-018-9649-7

At a glance: The STEP trials

Springer Medicine

Clinical and genetic findings of a Japanese patient with RP1-related autosomal recessive retinitis pigmentosa

Abstract

Purpose

Patient and methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Patient and methods

Results

Conclusion

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