Clinical and Genetic Findings in Korean Patients with Choroideremia
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: We share and analyze the clinical presentations and genotypes of Korean male patients and female carriers who visited our clinic. Methods: Six male patients and three female carriers with comprehensive ophthalmic examinations and next-generation sequencing were included. Detailed clinical features were identified using visual field (VF) test and multimodal imaging including color fundus photography, fundus autofluorescence (FAF), and optical coherence tomography (OCT). Results: Six male patients were diagnosed with choroideremia at the median age of 25 years. Before genetic testing, three patients (50.0%) were clinically diagnosed with choroideremia, while the other three patients (50.0%) with retinitis pigmentosa. Patients showed different types of hemizygous CHM variants, including two nonsense variants, c.715C>T:p.(Arg239*) and c.799C>T:p.(Arg267*); two frameshift variants, c.1584_1587del:p.(Val529Hisfs*7) and c.403_404del:p.(Asp135Phefs*9); one splicing variant c.1511-28_1511-2del; and one exon 2-8 duplication. The latter three variants were novel. Two female carriers had heterozygous exon 2-8 duplication and the other one female carrier had heterozygous nonsense variant c.715C>T:p. (Arg239*). Fundus showed diffuse yellow-whitish scleral reflex and granular pigmented lesions. FAF showed multiple patchy hypofluorescence lesions, sparing macula. OCT showed thinning of outer nuclear layer, ellipsoid zone, retinal pigment epithelium layer, choroid thickness, interlaminar bridges, outer retinal tubulations, and microcysts in the inner nuclear layer. VF showed ring scotoma pattern with small amount of remaining central field. Asymptomatic female carriers showed variable fundus findings and mild changes in OCT. Conclusions: A detailed description of the genotypes with three novel mutations and phenotypes of six choroideremia patients and three CHM mutation female carriers are presented.
Abstract
Purpose: We share and analyze the clinical presentations and genotypes of Korean male patients and female carriers who visited our clinic. Methods: Six male patients and three female carriers with comprehensive ophthalmic examinations and next-generation sequencing were included. Detailed clinical features were identified using visual field (VF) test and multimodal imaging including color fundus photography, fundus autofluorescence (FAF), and optical coherence tomography (OCT). Results: Six male patients were diagnosed with choroideremia at the median age of 25 years. Before genetic testing, three patients (50.0%) were clinically diagnosed with choroideremia, while the other three patients (50.0%) with retinitis pigmentosa. Patients showed different types of hemizygous CHM variants, including two nonsense variants, c.715C>T:p.(Arg239*) and c.799C>T:p.(Arg267*); two frameshift variants, c.1584_1587del:p.(Val529Hisfs*7) and c.403_404del:p.(Asp135Phefs*9); one splicing variant c.1511-28_1511-2del; and one exon 2-8 duplication. The latter three variants were novel. Two female carriers had heterozygous exon 2-8 duplication and the other one female carrier had heterozygous nonsense variant c.715C>T:p. (Arg239*). Fundus showed diffuse yellow-whitish scleral reflex and granular pigmented lesions. FAF showed multiple patchy hypofluorescence lesions, sparing macula. OCT showed thinning of outer nuclear layer, ellipsoid zone, retinal pigment epithelium layer, choroid thickness, interlaminar bridges, outer retinal tubulations, and microcysts in the inner nuclear layer. VF showed ring scotoma pattern with small amount of remaining central field. Asymptomatic female carriers showed variable fundus findings and mild changes in OCT. Conclusions: A detailed description of the genotypes with three novel mutations and phenotypes of six choroideremia patients and three CHM mutation female carriers are presented.
참고문헌 (31)
- MacDonald IM, "Choroideremia : new findings from ocular pathology and review of recent literature", Surv Ophthalmol, 54, pp.401~407 (2009)
- Preising M, "Rab escort protein 1(REP1)in intracellular traffic : a functional and pathophysiological overview", Ophthalmic Genet, 25, pp.101~110 (2004)
- Zhang AY, "choroideremia is a systemic disease with lymphocyte crystals and plasma lipid and RBC membrane abnormalities", Invest Ophthalmol Vis Sci, 56, pp.8158~8165 (2015)
- Lam BL, "Choroideremia gene therapy", Int Ophthalmol Clin, 61, pp.185~193 (2021)
- MacDonald IM, "GeneReviews®" (1993), University of Washington
- Roberts MF, "Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia", Br J Ophthalmol, 86, pp.658~662 (2002)
- Jauregui R, "Spectrum of disease severity and phenotype in choroideremia carriers", Am J Ophthalmol, 207, pp.77~86 (2019)
- Bonilha VL, "Choroideremia : analysis of the retina from a female symptomatic carrier", Ophthalmic Genet, 29, pp.99~110 (2008)
- Khan KN, "Clinical and genetic features of choroideremia in childhood", Ophthalmology, 123, pp.2158~2165 (2016)
- Ma DJ, "Whole-exome sequencing in 168 Korean patients with inherited retinal degeneration", BMC Med Genomics, 14, pp.74~ (2021)
- Jin Ha Kim, "Clinical Manifestations and Genetic Analysis of 5 Korean Choroideremia Patients Initially Diagnosed With Retinitis Pigmentosa", Journal of Korean Medical Science, 37(3), pp.1~8 (2022), 대한의학회[DOI]
- 배건호, "Identification of Pathogenic Variants in the CHM Gene in Two Korean Patients With Choroideremia", Annals of Laboratory Medicine, 37(5), pp.438~442 (2017), 대한진단검사의학회
- O SJ, "A case of choroideremia with recurrent anterior uveitis", Korean J Ophthalmol, 17, pp.55~62 (2003)
- 김민석, "Genetic Mutation Profiles in Korean Patients with Inherited Retinal Diseases", Journal of Korean Medical Science, 34(21), pp.1~11 (2019), 대한의학회
- Schmitz-Valckenberg S, "Fundus autofluorescence imaging : review and perspectives", Retina, 28, pp.385~409 (2008)
- Ach T, "Quantitative autofluorescence and cell density maps of the human retinal pigment epithelium", Invest Ophthalmol Vis Sci, 55, pp.4832~4841 (2014)
- Dysli C, "Autofluorescence lifetimes in patients with choroideremia identify photoreceptors in areas with retinal pigment epithelium atrophy", Invest Ophthalmol Vis Sci, 57, pp.6714~6721 (2016)
- Jolly JK, "A qualitative and quantitative assessment of fundus autofluorescence patterns in patients with choroideremia", Invest Ophthalmol Vis Sci, 57, pp.4498~4503 (2016)
- Zweifel SA, "Outer retinal tubulation : a novel optical coherence tomography finding", Arch Ophthalmol, 127, pp.1596~1602 (2009)
- Xue K, "Correlation of optical coherence tomography and autofluorescence in the outer retina and choroid of patients with choroideremia", Invest Ophthalmol Vis Sci, 57, pp.3674~3684 (2016)
- Syed R, "High-resolution images of retinal structure in patients with choroideremia", Invest Ophthalmol Vis Sci, 54, pp.950~961 (2013)
- Heon E, "Visual function and central retinal structure in choroideremia", Invest Ophthalmol Vis Sci, 57, pp.OCT377~87 (2016)
- Lazow MA, "Transition zones between healthy and diseased retina in choroideremia(CHM)and Stargardt disease(STGD)as compared to retinitis pigmentosa(RP)", Invest Ophthalmol Vis Sci, 52, pp.9581~9590 (2011)
- Sun LW, "Multimodal imaging of photoreceptor structure in choroideremia", PLoS One, 11, pp.e0167526~ (2016)
- Jacobson SG, "Remodeling of the human retina in choroideremia : rab escort protein 1(REP-1)mutations", Invest Ophthalmol Vis Sci, 47, pp.4113~4120 (2006)
- Genead MA, "Cystic macular oedema on spectral-domain optical coherence tomography in choroideremia patients without cystic changes on fundus examination", Eye(Lond), 25, pp.84~90 (2011)
- Murro V, "Optical coherence tomography(OCT)features of cystoid spaces in choroideremia(CHM)", Graefes Arch Clin Exp Ophthalmol, 257, pp.2655~2663 (2019)
- McCulloch C, "Choroideremia : a clinical and pathologic review", Trans Am Ophthalmol Soc, 67, pp.142~195 (1969)
- Di Giosaffatte N, "A novel hypothesis on choroideremia-manifesting female carriers:could CHM in-frame variants exert a dominant negative effect? A case report", Genes (Basel), 13, pp.1268~ (2022)
- Mitsios A, "Choroideremia : from genetic and clinical phenotyping to gene therapy and future treatments", Ther Adv Ophthalmol, 10, pp.2515841418817490~ (2018)
- Zinkernagel MS, "Recent advances and future prospects in choroideremia", Clin Ophthalmol, 9, pp.2195~2200 (2015)