Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Clinical Assessment
2.2. Genetic Analyses
2.3. Clinical Subgroups
3. Results
3.1. Phenotypic Features of Patients
3.2. Genotypes of Patients
3.3. Genotype–Phenotype Correlation
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Freund, C.L.; Gregory-Evans, C.Y.; Furukawa, T.; Papaioannou, M.; Looser, J.; Ploder, L.; Bellingham, J.; Ng, D.; Herbrick, J.A.; Duncan, A.; et al. Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor. Cell 1997, 91, 543–553. [Google Scholar] [CrossRef] [PubMed]
- Furukawa, T.; Morrow, E.M.; Cepko, C.L. Crx, a novel otx-like homeobox gene, shows photoreceptor-specific expression and regulates photoreceptor differentiation. Cell 1997, 91, 531–541. [Google Scholar] [CrossRef] [PubMed]
- Chen, S.; Wang, Q.L.; Nie, Z.; Sun, H.; Lennon, G.; Copeland, N.G.; Gilbert, D.J.; Jenkins, N.A.; Zack, D.J. Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes. Neuron 1997, 19, 1017–1030. [Google Scholar] [CrossRef] [PubMed]
- Evans, K.; Fryer, A.; Inglehearn, C.; Duvall-Young, J.; Whittaker, J.L.; Gregory, C.Y.; Butler, R.; Ebenezer, N.; Hunt, D.M.; Bhattacharya, S. Genetic linkage of cone-rod retinal dystrophy to chromosome 19q and evidence for segregation distortion. Nat. Genet. 1994, 6, 210–213. [Google Scholar] [CrossRef]
- Stone, E.M. Leber congenital amaurosis—A model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture. Am. J. Ophthalmol. 2007, 144, 791–811. [Google Scholar] [CrossRef]
- Huang, L.; Xiao, X.; Li, S.; Jia, X.; Wang, P.; Sun, W.; Xu, Y.; Xin, W.; Guo, X.; Zhang, Q. Molecular genetics of cone-rod dystrophy in Chinese patients: New data from 61 probands and mutation overview of 163 probands. Exp. Eye Res. 2016, 146, 252–258. [Google Scholar] [CrossRef]
- Daiger, S.P.; Sullivan, L.S.; Bowne, S.J. Genes and mutations causing retinitis pigmentosa. Clin. Genet. 2013, 84, 132–141. [Google Scholar] [CrossRef]
- Hull, S.; Arno, G.; Plagnol, V.; Chamney, S.; Russell-Eggitt, I.; Thompson, D.; Ramsden, S.C.; Black, G.C.; Robson, A.; Holder, G.E.; et al. The phenotypic variability of retinal dystrophies associated with mutations in CRX, with report of a novel macular dystrophy phenotype. Invest. Ophthalmol. Vis. Sci. 2014, 55, 6934–6944. [Google Scholar] [CrossRef]
- Yi, Z.; Xiao, X.; Li, S.; Sun, W.; Zhang, Q. Pathogenicity discrimination and genetic test reference for CRX variants based on genotype-phenotype analysis. Exp. Eye Res. 2019, 189, 107846. [Google Scholar] [CrossRef]
- Fujinami-Yokokawa, Y.; Fujinami, K.; Kuniyoshi, K.; Hayashi, T.; Ueno, S.; Mizota, A.; Shinoda, K.; Arno, G.; Pontikos, N.; Yang, L.; et al. Clinical and Genetic Characteristics of 18 Patients from 13 Japanese Families with CRX-associated retinal disorder: Identification of Genotype-phenotype Association. Sci. Rep. 2020, 10, 9531. [Google Scholar] [CrossRef]
- Nishiguchi, K.M.; Kunikata, H.; Fujita, K.; Hashimoto, K.; Koyanagi, Y.; Akiyama, M.; Ikeda, Y.; Momozawa, Y.; Sonoda, K.H.; Murakami, A.; et al. Association of CRX genotypes and retinal phenotypes confounded by variable expressivity and electronegative electroretinogram. Clin. Exp. Ophthalmol. 2020, 48, 644–657. [Google Scholar] [CrossRef] [PubMed]
- Berger, W.; Kloeckener-Gruissem, B.; Neidhardt, J. The molecular basis of human retinal and vitreoretinal diseases. Prog. Retin. Eye Res. 2010, 29, 335–375. [Google Scholar] [CrossRef] [PubMed]
- Hood, D.C.; Bach, M.; Brigell, M.; Keating, D.; Kondo, M.; Lyons, J.S.; Marmor, M.F.; McCulloch, D.L.; Palmowski-Wolfe, A.M.; International Society for Clinical Electrophysiology of Vision. ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc. Ophthalmol. 2012, 124, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Marmor, M.F.; Fulton, A.B.; Holder, G.E.; Miyake, Y.; Brigell, M.; Bach, M.; International Society for Clinical Electrophysiology of Vision. ISCEV Standard for full-field clinical electroretinography (2008 update). Doc. Ophthalmol. 2009, 118, 69–77. [Google Scholar] [CrossRef] [PubMed]
- McCulloch, D.L.; Marmor, M.F.; Brigell, M.G.; Hamilton, R.; Holder, G.E.; Tzekov, R.; Bach, M. ISCEV Standard for full-field clinical electroretinography (2015 update). Doc. Ophthalmol. 2015, 130, 1–12. [Google Scholar] [CrossRef] [PubMed]
- Robson, A.G.; Nilsson, J.; Li, S.; Jalali, S.; Fulton, A.B.; Tormene, A.P.; Holder, G.E.; Brodie, S.E. ISCEV guide to visual electrodiagnostic procedures. Doc. Ophthalmol. 2018, 136, 1–26. [Google Scholar] [CrossRef]
- Kim, M.S.; Joo, K.; Seong, M.W.; Kim, M.J.; Park, K.H.; Park, S.S.; Woo, S.J. Genetic Mutation Profiles in Korean Patients with Inherited Retinal Diseases. J. Korean Med. Sci. 2019, 34, e161. [Google Scholar] [CrossRef]
- Jin, K.W.; Joo, K.; Woo, S.J. Clinical Characterization of Korean Patients with Pseudoxanthoma Elasticum and Angioid Streaks. Genes 2021, 12, 1207. [Google Scholar] [CrossRef]
- Richards, S.; Aziz, N.; Bale, S.; Bick, D.; Das, S.; Gastier-Foster, J.; Grody, W.W.; Hegde, M.; Lyon, E.; Spector, E.; et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 2015, 17, 405–424. [Google Scholar] [CrossRef]
- Li, Q.; Wang, K. InterVar: Clinical Interpretation of Genetic Variants by the 2015 ACMG-AMP Guidelines. Am. J. Hum. Genet. 2017, 100, 267–280. [Google Scholar] [CrossRef]
- Surl, D.; Shin, S.; Lee, S.T.; Choi, J.R.; Lee, J.; Byeon, S.H.; Han, S.H.; Lim, H.T.; Han, J. Copy number variations and multiallelic variants in Korean patients with Leber congenital amaurosis. Mol. Vis. 2020, 26, 26–35. [Google Scholar] [PubMed]
- Han, J.; Rim, J.H.; Hwang, I.S.; Kim, J.; Shin, S.; Lee, S.T.; Choi, J.R. Diagnostic application of clinical exome sequencing in Leber congenital amaurosis. Mol. Vis. 2017, 23, 649–659. [Google Scholar] [PubMed]
- Swain, P.K.; Chen, S.; Wang, Q.L.; Affatigato, L.M.; Coats, C.L.; Brady, K.D.; Fishman, G.A.; Jacobson, S.G.; Swaroop, A.; Stone, E.; et al. Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration. Neuron 1997, 19, 1329–1336. [Google Scholar] [CrossRef] [PubMed]
- Arai, Y.; Maeda, A.; Hirami, Y.; Ishigami, C.; Kosugi, S.; Mandai, M.; Kurimoto, Y.; Takahashi, M. Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations. J. Ophthalmol. 2015, 2015, 819760. [Google Scholar] [CrossRef]
- Jin, Z.B.; Mandai, M.; Yokota, T.; Higuchi, K.; Ohmori, K.; Ohtsuki, F.; Takakura, S.; Itabashi, T.; Wada, Y.; Akimoto, M.; et al. Identifying pathogenic genetic background of simplex or multiplex retinitis pigmentosa patients: A large scale mutation screening study. J. Med. Genet. 2008, 45, 465–472. [Google Scholar] [CrossRef]
- Jespersgaard, C.; Fang, M.; Bertelsen, M.; Dang, X.; Jensen, H.; Chen, Y.; Bech, N.; Dai, L.; Rosenberg, T.; Zhang, J.; et al. Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. Sci. Rep. 2019, 9, 1219. [Google Scholar] [CrossRef]
- Nasser, F.; Kurtenbach, A.; Kohl, S.; Obermaier, C.; Stingl, K.; Zrenner, E. Retinal dystrophies with bull’s-eye maculopathy along with negative ERGs. Doc. Ophthalmol. 2019, 139, 45–57. [Google Scholar] [CrossRef]
- Eisenberger, T.; Neuhaus, C.; Khan, A.O.; Decker, C.; Preising, M.N.; Friedburg, C.; Bieg, A.; Gliem, M.; Charbel Issa, P.; Holz, F.G.; et al. Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: The example of retinal dystrophies. PLoS ONE 2013, 8, e78496. [Google Scholar] [CrossRef]
- Swaroop, A.; Wang, Q.L.; Wu, W.; Cook, J.; Coats, C.; Xu, S.; Chen, S.; Zack, D.J.; Sieving, P.A. Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: Direct evidence for the involvement of CRX in the development of photoreceptor function. Hum. Mol. Genet. 1999, 8, 299–305. [Google Scholar] [CrossRef]
- Perrault, I.; Hanein, S.; Gerber, S.; Barbet, F.; Dufier, J.L.; Munnich, A.; Rozet, J.M.; Kaplan, J. Evidence of autosomal dominant Leber congenital amaurosis (LCA) underlain by a CRX heterozygous null allele. J. Med. Genet. 2003, 40, e90. [Google Scholar] [CrossRef]
- Rivolta, C.; Peck, N.E.; Fulton, A.B.; Fishman, G.A.; Berson, E.L.; Dryja, T.P. Novel frameshift mutations in CRX associated with Leber congenital amaurosis. Hum. Mutat. 2001, 18, 550–551. [Google Scholar] [CrossRef] [PubMed]
- Itabashi, T.; Wada, Y.; Sato, H.; Kawamura, M.; Shiono, T.; Tamai, M. Novel 615delC mutation in the CRX gene in a Japanese family with cone-rod dystrophy. Am. J. Ophthalmol. 2004, 138, 876–877. [Google Scholar] [CrossRef] [PubMed]
- Kitiratschky, V.B.; Nagy, D.; Zabel, T.; Zrenner, E.; Wissinger, B.; Kohl, S.; Jagle, H. Cone and cone-rod dystrophy segregating in the same pedigree due to the same novel CRX gene mutation. Br. J. Ophthalmol. 2008, 92, 1086–1091. [Google Scholar] [CrossRef]
- Freund, C.L.; Wang, Q.L.; Chen, S.; Muskat, B.L.; Wiles, C.D.; Sheffield, V.C.; Jacobson, S.G.; McInnes, R.R.; Zack, D.J.; Stone, E.M. De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. Nat. Genet. 1998, 18, 311–312. [Google Scholar] [CrossRef] [PubMed]
- Oishi, M.; Oishi, A.; Gotoh, N.; Ogino, K.; Higasa, K.; Iida, K.; Makiyama, Y.; Morooka, S.; Matsuda, F.; Yoshimura, N. Comprehensive molecular diagnosis of a large cohort of Japanese retinitis pigmentosa and Usher syndrome patients by next-generation sequencing. Invest. Ophthalmol. Vis. Sci. 2014, 55, 7369–7375. [Google Scholar] [CrossRef]
- Rivolta, C.; Berson, E.L.; Dryja, T.P. Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX. Hum. Mutat. 2001, 18, 488–498. [Google Scholar] [CrossRef] [PubMed]
- Brzezinski, J.A.; Reh, T.A. Photoreceptor cell fate specification in vertebrates. Development 2015, 142, 3263–3273. [Google Scholar] [CrossRef]
- Corbo, J.C.; Lawrence, K.A.; Karlstetter, M.; Myers, C.A.; Abdelaziz, M.; Dirkes, W.; Weigelt, K.; Seifert, M.; Benes, V.; Fritsche, L.G.; et al. CRX ChIP-seq reveals the cis-regulatory architecture of mouse photoreceptors. Genome Res. 2010, 20, 1512–1525. [Google Scholar] [CrossRef]
- Cherry, T.J.; Yang, M.G.; Harmin, D.A.; Tao, P.; Timms, A.E.; Bauwens, M.; Allikmets, R.; Jones, E.M.; Chen, R.; De Baere, E.; et al. Mapping the cis-regulatory architecture of the human retina reveals noncoding genetic variation in disease. Proc. Natl. Acad. Sci. USA 2020, 117, 9001–9012. [Google Scholar] [CrossRef]
- Burglin, T.R.; Affolter, M. Homeodomain proteins: An update. Chromosoma 2016, 125, 497–521. [Google Scholar] [CrossRef]
- Chau, K.Y.; Chen, S.; Zack, D.J.; Ono, S.J. Functional domains of the cone-rod homeobox (CRX) transcription factor. J. Biol. Chem. 2000, 275, 37264–37270. [Google Scholar] [CrossRef] [PubMed]
- Fei, Y.; Hughes, T.E. Nuclear trafficking of photoreceptor protein crx: The targeting sequence and pathologic implications. Investig. Ophthalmol. Vis. Sci. 2000, 41, 2849–2856. [Google Scholar]
- Silva, E.; Yang, J.M.; Li, Y.; Dharmaraj, S.; Sundin, O.H.; Maumenee, I.H. A CRX null mutation is associated with both Leber congenital amaurosis and a normal ocular phenotype. Invest. Ophthalmol. Vis. Sci. 2000, 41, 2076–2079. [Google Scholar] [PubMed]
- Ibrahim, M.T.; Alarcon-Martinez, T.; Lopez, I.; Fajardo, N.; Chiang, J.; Koenekoop, R.K. A complete, homozygous CRX deletion causing nullizygosity is a new genetic mechanism for Leber congenital amaurosis. Sci. Rep. 2018, 8, 5034. [Google Scholar] [CrossRef]
- Yahya, S.; Smith, C.E.L.; Poulter, J.A.; McKibbin, M.; Arno, G.; Ellingford, J.; Kampjarvi, K.; Khan, M.I.; Cremers, F.P.M.; Hardcastle, A.J.; et al. Late-Onset Autosomal Dominant Macular Degeneration Caused by Deletion of the CRX Gene. Ophthalmology 2022, 130, 68–76. [Google Scholar] [CrossRef]
- Clanor, P.B.; Buchholz, C.N.; Hayes, J.E.; Friedman, M.A.; White, A.M.; Enke, R.A.; Berndsen, C.E. Structural and functional analysis of the human cone-rod homeobox transcription factor. Proteins 2022, 90, 1584–1593. [Google Scholar] [CrossRef]
Patient No. | CRX Variants | Molecularly Raised Inheritance | Inheritance Based on Family History | Sex | Age at Onset (years) | Age at Examination (years) | Symptom | Initial Decimal BCVA (logMAR Unit) | Refractive Errors | Phenotype Subgroup | Fundus Appearance | ERG | VF | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Right | Left | Right | Left | ||||||||||||
1 | c.101-1G>A | AD | Sporadic | F | 34 | 35 | Decreased vision | 0.2 (0.7) | 0.3 (0.52) | −6.00 | −7.00 | CORD | Mild RPE irregularity in macula | More prominent reduction in cone response, negative ERG | Paracentral ring scotoma |
2 | c.101-1G>A c.122G>A | AR | AR | M | Birth | 35 | Decreased vision | HM | HM | 5.50 | 6.50 | LCA | Central macular atrophy, peripheral retinal atrophy, bone spicules | Undetectable | N/A |
3 | c.118C>T | AD | Sporadic | F | 25 | 31 | Decreased vision | 0.5 (0.3) | 0.4 (0.4) | −1.50 | −1.50 | CORD | Mild RPE irregularity in macula, annular depigmentation along the arcade | More prominent reduction in cone response, negative ERG | Paracentral ring scotoma |
4 | c.121C>T | AD | AD | F | 4 | 21 | Decreased vision | 0.2 (0.7) | 0.2 (0.7) | −8.50 | −9.50 | CORD | Mild RPE irregularity in macula | Severe reduction in cone response, negative ERG | Central scotoma |
5 | c.128G>A | AD | AD | M | 45 | 46 | Visual distortion | 1.0 (0.0) | 1.0 (0.0) | −9.5 | −9.50 | MD | Ring of RPE atrophy in macula | Negative ERG | Cecocentral scotoma |
6 | c.193G>C | AD | Sporadic | M | 40 | 78 | Decreased vision, photophobia | 0.3 (0.52) | 0.4 (0.4) | 1.25 | 1.25 | MD | Ring of RPE atrophy in macula, mild granularity in peripheral retinae | Normal ERG | N/A |
7 | c.193G>C | AD | Sporadic | M | 50 | 51 | Decreased vision | HM | 0.5 (0.3) | −6.00 | −7.00 | CORD | Round RPE atrophy in macula, moderate granularity in peripheral retinae | Severe reduction in cone response, negative ERG | Central scotoma |
8 | c.443del | AD | AD | F | Birth | 7 mo | Poor eye contact | USCM | USCM | 2.50 | 2.50 | LCA | Blond fundus, peripheral white punctate lesions | Undetectable | N/A |
9 | c.684G>C | AD | AD | M | 30 | 63 | Night blindness | 0.5 (0.3) | 0.4 (0.4) | −0.50 | −0.50 | RP | Peripheral retinal atrophy, bone spicule, central atrophy of right macula, attenuated arterioles | Undetectable | Central tunnel |
10 | c.898T>C | AD | Sporadic | M | 39 | 42 | Decreased vision | 0.15 (0.82) | 0.15 (0.82) | −2.50 | −3.00 | CORD | RPE irregularity in macula | More prominent reduction in cone response, negative ERG | Central scotoma |
11 | c.898T>C | AD | Sporadic | M | 30 | 32 | Visual disturbance | 0.9 (0.05) | 0.8 (0.10) | −9.00 | −9.00 | CORD | RPE irregularity in macula | More prominent reduction in cone response, negative ERG | N/A |
Pt | Nucleotide | Amino Acid | CADD | Polyphen-2 | SIFT | gnomAD | ClinVar | ACMG | Novel Variant |
---|---|---|---|---|---|---|---|---|---|
1 | c.101-1G>A | - | 33 | NA | NA | NF | No interpretation for the single variant | P | Surl [21] However, novel as solitary |
2 | c.101-1G>A c.122G>A | - p.(Arg41Gln) | 33 28.5 | NA 0.998 | NA 0 | NF 1/31396 | P P | P LP | Surl [21] Swain [23] |
3 | c.118C>T | p.(Arg40Trp) | 28.9 | 0.996 | 0 | 1/250660 | P | P | Arai [24] |
4 | c.121C>T | p.(Arg41Trp) | 25.6 | 0.996 | 0 | 2/251204 | P | P | Swain [23] |
5 | c.128G>A | p.(Arg43His) | 28.4 | 0.995 | 0 | 1/251318 | P | P | Yi [9] |
6 | c.193G>C | p.(Asp65His) | 26.6 | 0.998 | 0 | NF | P | LP | Jin [25] |
7 | |||||||||
8 | c.443del | p.(Gly148Alafs*39) | 28.3 | NA | NA | NF | P | P | Han [22] |
9 | c.684G>C | p.(Gln228His) | 16.75 | 0.917 | 0.04 | 2/151064 | LP | US | Jespersgaard [26] |
10 | c.898T>C | p.(*300Glnext*118) | 16.07 | NA | NA | NF | LP | LP | Novel |
11 |
Author | Publication Year | Number of Variants and Patients | Nationality | Genotype–Phenotype Correlation |
---|---|---|---|---|
Hull et al. [8] | 2014 | 10 variants of 18 patients | UK | No evident association between age of onset and position or type of CRX mutation. |
Yi et al. [9] | 2019 | 12 pathogenic variants of 18 affected patients (total 24 variants including benign variants) | China | Approximately half of heterozygous missense variants are likely benign, heterozygous truncating variants affecting the homeodomain are likely benign. Truncating mutations after the homeodomain are likely associated with a more severe phenotype. |
Fujinami et al. [10] | 2020 | 8 variants of 18 patients | Japan | There seems to be a trend between phenotype and genotype (subgroups considering mutation type and zygosity). |
Nishiguchi et al. [11] | 2020 | 6 variants of 21 patients | Japan | Heterozygous mutations within or downstream of the homeobox domain in CRX relate to the different retinal phenotypes |
Our study | 2022 | 9 variants of 11 patients (total 13 variants of 15 patients including benign variants) | Korea | All mutations within the homeodomain are missense mutations, and most are expressed as cone-rod dystrophy or macular dystrophy. Most variants after the homeodomain are truncating mutations, and the phenotypes are diverse |
Nucleotide Change | Amino Acid Change | Reference | Nationality | Zygosity | Phenotype | N of Affected Cases | Age of Symptom Onset | First Report |
---|---|---|---|---|---|---|---|---|
c.101-1G>A | N/A | This study | Korea | Heterozygous | CORD | 1 | 34 | This study |
c.101-1G>A c.122G>A | N/A p.Arg41Gln | This study | Korea | Compound heterozygous | LCA | 1 | Birth | [21] [23] |
c.118C>T | p.Arg40Trp | [10] | Japan | Heterozygous | CORD | 5 | 30, 35, 56, NA, NA | [24] |
[9] | China | Heterozygous | RP | 1 | NA | |||
This study | Korea | Heterozygous | CORD | 1 | 25 | |||
c.121C>T | p.Arg41Trp | [10] | Japan | Heterozygous | CORD | 3 | 60, NA, NA | [23] |
[11] † | Japan | Heterozygous | CORD † | 11 | 29, 30, 34, 39, 40, 45, 47, 53, 54, 58, 71 | |||
[9] | China | Heterozygous | CORD | 1 | NA | |||
This study | Korea | Heterozygous | CORD | 1 | 4 | |||
[8] | UK | Heterozygous | RP | 1 | 3.5 | |||
Heterozygous | MD | 1 | 53 | |||||
c.127C>T | p.Arg43Cys | [10] | Japan | Heterozygous | CORD | 2 | 75, 77 | [6] |
[11] † | Japan | Heterozygous | CORD † | 1 | 16 | |||
[9] | China | Heterozygous | CORD | 1 | 36 | |||
c.128G>A | p.Arg43His | [9] | China | Heterozygous | LCA | 1 | ECH | [9] |
[10] | Japan | Heterozygous | MD | 2 | 31, 62 | |||
This study | Korea | Heterozygous | MD | 1 | 45 | |||
c.193G>C | p.Asp65His | [10] | Japan | Homozygous | RP | 2 | 37, NA | [25] |
This study | Korea | Heterozygous | MD | 1 | 40 | |||
CORD | 1 | 50 | ||||||
c.268C>T | p.Arg90Trp | [10] | Japan | Heterozygous | CORD | 1 | 45 | [29] |
c.272G>A | p.Arg91Lys | [8] | UK | Heterozygous | MD | 1 | 35 | [8] |
c.434del | p.Pro145Leufs*42 | [10] | Japan | Heterozygous | RP | 1 | 15 | [10] |
c.443del | p.Gly148Alafs*39 | This study | Korea | Heterozygous | LCA | 1 | Birth | [22] |
c.509del | p.Pro170Leufs*17 | [9] | China | Heterozygous | LCA | 2 | ECH, ECH | [30] |
c.557dup | p.Thr187Aspfs*49 | [9] | China | Heterozygous | CORD | 2 | NA, NA | [9] |
c.568_590del | p.Pro190Glyfs*38 | [8] | UK | Heterozygous | CORD | 3 | 12, 12, 14 | [8] |
c.570del | p.Tyr191Metfs*3 | [8] | UK | Heterozygous | LCA | 2 | Birth | [8] |
c.571del | p.Tyr191Metfs*3 | [8] | UK | Heterozygous | LCA | 1 | 3mo | [31] |
c.573T>G | p.Tyr191* | [9] | China | Heterozygous | LCA | 1 | 0.3 | [9] |
c.582del | p.Tyr195Thrfs*24 | [8] | UK | Heterozygous | MD | 1 | 42 | [8] |
c.590del | p.Pro197Alafs*22 | [10] | Japan | Heterozygous | CORD | 2 | 30, 45 | [10] |
c.605del | p.Cys202Serfs*17 | [8] | UK | Heterozygous | MD | 1 | 50 | [8] |
COD | 1 | 45 | ||||||
c.615del | p.Ser206Profs*13 | [11] † | Japan | Heterozygous | RP † | 1 | 40 | [32] |
c.624T>G | p.Tyr208* | [8] | UK | Heterozygous | LCA | 1 | Birth | [5] |
Heterozygous | RP | 1 | 6 | |||||
c.636del | p.Ser213Profs*6 | [9] | China | Heterozygous | CORD | 1 | 12 | [33] |
c.639del | p.Tyr214Ilefs*5 | [11] † | Japan | Heterozygous | RP † | 1 | 6 | [11] |
c.642T>G | p.Tyr214* | [9] | China | Heterozygous | LCA | 2 | 0.4, ECH | [9] |
c.650del | p.Gly217Alafs*2 | [9] | China | Heterozygous | LCA | 2 | ECH, ECH | [34] |
c.684G>C | p.Gln228His | This study | Korea | Heterozygous | RP | 1 | 30 | [26] |
c.692del | p.Gly231Alafs*140 | [9] | China | Heterozygous | LCA | 2 | ECH, ECH | [9] |
c.727G>T | p.Gly243* | [11] † | Japan | Heterozygous | CORD † | 2 | 68, 51 | [11] |
RP † | 1 | 45 | ||||||
c.774T>A | p.Tyr258* | [8] | UK | Heterozygous | MD | 2 | 49, 50 | [8] |
CORD | 1 | 32 | ||||||
c.787_790del | p.Pro263Trpfs*107 | [9] | China | Heterozygous | LCA | 2 | 0.4, NA | [9] |
c.821del | p.Gly274Alafs*97 | [8] | UK | Heterozygous | CORD | 1 | 11 | [8] |
c.897G>C | p.Leu299Phe | [11] † | Japan | Heterozygous | RP † | 1 | 31 | [35] |
c.898T>C | p.*300Glnext*118 | This study | Korea | Heterozygous | CORD | 2 | 30,39 | This study |
CORD (N = 44) | MD (N = 10) | RCD (N = 11) | LCA * (N = 18) | p Value | |
---|---|---|---|---|---|
Age at symptom onset (years) | 39.0 ± 18.8 | 45.7 ± 9.1 | 23.7 ± 16.2 | 0.1 ± 0.2 | <0.01 † |
BCVA of better eye (logMAR unit) | 0.6 ± 0.5 | 0.4 ± 0.4 | 0.8 ± 0.8 | 2.4 ± 0.6 | <0.01 ‡ |
China (N = 18) | Japan (N = 36) | Korea (N = 11) | UK (N = 18) | p Value | |
---|---|---|---|---|---|
Age at symptom onset | 3.8 ± 10.2 | 43.7 ± 17.3 | 29.7 ± 16.4 | 23.0 ± 20.8 | <0.01 † |
BCVA of better eye (logMAR unit) | 1.3 ± 1.0 | 0.5 ± 0.5 | 0.8 ± 0.9 | 1.3 ± 1.0 | <0.01 ‡ |
Phenotype | N/A | ||||
COD or CORD | 5 (27.8%) | 27 (75.0%) | 6 (54.5%) | 6 (33.3%) | |
MD | 0 | 2 (5.6%) | 2 (18.2%) | 6 (33.3%) | |
RP or RCD | 1 (5.6%) | 7 (19.4%) | 1 (9.1%) | 2 (11.1%) | |
LCA | 12 (66.7%) | 0 | 2 (18.2%) | 4 (22.2%) |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kim, D.G.; Joo, K.; Han, J.; Choi, M.; Kim, S.-W.; Park, K.H.; Park, S.J.; Lee, C.S.; Byeon, S.H.; Woo, S.J. Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans. Genes 2023, 14, 1057. https://doi.org/10.3390/genes14051057
Kim DG, Joo K, Han J, Choi M, Kim S-W, Park KH, Park SJ, Lee CS, Byeon SH, Woo SJ. Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans. Genes. 2023; 14(5):1057. https://doi.org/10.3390/genes14051057
Chicago/Turabian StyleKim, Dong Geun, Kwangsic Joo, Jinu Han, Mihyun Choi, Seong-Woo Kim, Kyu Hyung Park, Sang Jun Park, Christopher Seungkyu Lee, Suk Ho Byeon, and Se Joon Woo. 2023. "Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans" Genes 14, no. 5: 1057. https://doi.org/10.3390/genes14051057
APA StyleKim, D. G., Joo, K., Han, J., Choi, M., Kim, S.-W., Park, K. H., Park, S. J., Lee, C. S., Byeon, S. H., & Woo, S. J. (2023). Genotypic Profile and Clinical Characteristics of CRX-Associated Retinopathy in Koreans. Genes, 14(5), 1057. https://doi.org/10.3390/genes14051057