Next-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses
Abstract Background To report the clinical and genetic findings from seven Chinese patients with choroideremia. Methods Five hundred seventy-eight patients with a clinically suspected diagnosis of retinitis pigmentosa (RP) underwent comprehensive ophthalmic examinations. Next-generation sequencing (...
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BMC
2020-06-01
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| Series: | BMC Ophthalmology |
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| Online Access: | http://link.springer.com/article/10.1186/s12886-020-01478-x |
| _version_ | 1818791858494504960 |
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| author | Feng-Juan Gao Guo-Hong Tian Fang-Yuan Hu Dan-Dan Wang Jian-Kang Li Qing Chang Fang Chen Ge-Zhi Xu Wei Liu Ji-Hong Wu |
| author_facet | Feng-Juan Gao Guo-Hong Tian Fang-Yuan Hu Dan-Dan Wang Jian-Kang Li Qing Chang Fang Chen Ge-Zhi Xu Wei Liu Ji-Hong Wu |
| author_sort | Feng-Juan Gao |
| collection | DOAJ |
| description | Abstract Background To report the clinical and genetic findings from seven Chinese patients with choroideremia. Methods Five hundred seventy-eight patients with a clinically suspected diagnosis of retinitis pigmentosa (RP) underwent comprehensive ophthalmic examinations. Next-generation sequencing (NGS) was performed on samples from all patients. Detailed clinical characteristics of the patients with choroideremia identified in this study were assessed using multimodal imaging. Results Seven patients with choroideremia were identified, and six novel variants in CHM (c.1960 T > C p.Ter654Gln, c.1257del p.Ile420*fs1, c.1103_1121delATGGCAACACTCCATTTTT p.Tyr368Cysfs35, c.1414-2A > T, and c.1213C > T p.Gln405Ter, c.117-1G > A) were revealed. All variants were deleterious mutations: two were frameshifts, two were nonsense mutations, two were splicing mutations, and one was a readthrough mutation. The clinical phenotypes of these patients were markedly heterogeneous, and they shared many common clinical features with RP, including night blindness, constriction of the visual field and gradually reduced visual acuity. However, patients with choroideremia showed pigment hypertrophy and clumping, and chorioretinal atrophy, and a majority of patients with choroideremia presented with retinal tubulations in the outer layer of the retina. Conclusions We provide a detailed description of the genotypes and phenotypes of seven patients with choroideremia who were accurately diagnosed using NGS. These findings provide a better understanding of the genetics and phenotypes of choroideremia. |
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| language | English |
| last_indexed | 2024-12-18T15:18:02Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
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| series | BMC Ophthalmology |
| spelling | doaj.art-fdb9e4a02fec4be4b2a418a1eeb844752022-12-21T21:03:29ZengBMCBMC Ophthalmology1471-24152020-06-012011810.1186/s12886-020-01478-xNext-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analysesFeng-Juan Gao0Guo-Hong Tian1Fang-Yuan Hu2Dan-Dan Wang3Jian-Kang Li4Qing Chang5Fang Chen6Ge-Zhi Xu7Wei Liu8Ji-Hong Wu9Eye Institute, Eye and ENT Hospital, Fudan UniversityEye Institute, Eye and ENT Hospital, Fudan UniversityEye Institute, Eye and ENT Hospital, Fudan UniversityEye Institute, Eye and ENT Hospital, Fudan UniversityBGI-ShenzhenEye Institute, Eye and ENT Hospital, Fudan UniversityBGI-ShenzhenEye Institute, Eye and ENT Hospital, Fudan UniversityEye Institute, Eye and ENT Hospital, Fudan UniversityEye Institute, Eye and ENT Hospital, Fudan UniversityAbstract Background To report the clinical and genetic findings from seven Chinese patients with choroideremia. Methods Five hundred seventy-eight patients with a clinically suspected diagnosis of retinitis pigmentosa (RP) underwent comprehensive ophthalmic examinations. Next-generation sequencing (NGS) was performed on samples from all patients. Detailed clinical characteristics of the patients with choroideremia identified in this study were assessed using multimodal imaging. Results Seven patients with choroideremia were identified, and six novel variants in CHM (c.1960 T > C p.Ter654Gln, c.1257del p.Ile420*fs1, c.1103_1121delATGGCAACACTCCATTTTT p.Tyr368Cysfs35, c.1414-2A > T, and c.1213C > T p.Gln405Ter, c.117-1G > A) were revealed. All variants were deleterious mutations: two were frameshifts, two were nonsense mutations, two were splicing mutations, and one was a readthrough mutation. The clinical phenotypes of these patients were markedly heterogeneous, and they shared many common clinical features with RP, including night blindness, constriction of the visual field and gradually reduced visual acuity. However, patients with choroideremia showed pigment hypertrophy and clumping, and chorioretinal atrophy, and a majority of patients with choroideremia presented with retinal tubulations in the outer layer of the retina. Conclusions We provide a detailed description of the genotypes and phenotypes of seven patients with choroideremia who were accurately diagnosed using NGS. These findings provide a better understanding of the genetics and phenotypes of choroideremia.http://link.springer.com/article/10.1186/s12886-020-01478-xChoroideremiaCHMGene mutationsMolecular diagnosisOptical coherence tomography |
| spellingShingle | Feng-Juan Gao Guo-Hong Tian Fang-Yuan Hu Dan-Dan Wang Jian-Kang Li Qing Chang Fang Chen Ge-Zhi Xu Wei Liu Ji-Hong Wu Next-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses BMC Ophthalmology Choroideremia CHM Gene mutations Molecular diagnosis Optical coherence tomography |
| title | Next-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses |
| title_full | Next-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses |
| title_fullStr | Next-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses |
| title_full_unstemmed | Next-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses |
| title_short | Next-generation sequencing-based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses |
| title_sort | next generation sequencing based clinical diagnosis of choroideremia and comprehensive mutational and clinical analyses |
| topic | Choroideremia CHM Gene mutations Molecular diagnosis Optical coherence tomography |
| url | http://link.springer.com/article/10.1186/s12886-020-01478-x |
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