AIM：To analyze the influences of different genotypes（G11778A,T14484 C and G3460A） of Leber hereditary optic neuropathy（LHON） on visual prognosis. METHODS： After a systematic literature search,all relevant studie...AIM：To analyze the influences of different genotypes（G11778A,T14484 C and G3460A） of Leber hereditary optic neuropathy（LHON） on visual prognosis. METHODS： After a systematic literature search,all relevant studies evaluating the association between the three primary mutations of LHON and visual prognosis were included.All statistical tests were calculated with Revman 5.2 and STATA 12.0. RESULTS： Ten independent studies were included finally.A significant association between the three primary mutations and prognostic vision over 0.3 were found in G11778 A versus T14484 C [odds ratio（OR） =0.10,95% confidence interval（CI） =0.05-0.17,P 〈0.001],G11778 A versus G3460A（OR=0.18,95%CI=0.09-0.37,P 〈0.001） and T14484 C versus G3460A（OR =2.45,95% CI =1.10-5.48,P 〈0.05）.In addition,obtained by pairwise comparison,the vision during onset,age of onset and sex ratio of these three kinds of patients,have no statistical significance（P 〉0.05）.CONCLUSION： From pairwise comparison,we conclude that these three different genotypes of LHON are related to patients＇ visual prognosis.The T14484 C patients might have a best prognostic vision,G3460 A second,and G11778 A worst.And there is little relation between the three different genotypes and patients＇ vision,age of onset and sex ratio.展开更多
AIM:To investigate the foveal pit morphology changes in unaffected carriers and affected Leber’s hereditary optic neuropathy(LHON)patients with the G11778 A mutation from one family.METHODS:This study was a prospecti...AIM:To investigate the foveal pit morphology changes in unaffected carriers and affected Leber’s hereditary optic neuropathy(LHON)patients with the G11778 A mutation from one family.METHODS:This study was a prospective cross-sectional study.Both eyes from 16 family members(age from 9 to 47 y)with the G11778 A mutation were analyzed and compared with 1 eye from 20 normal control subjects.Eleven family members with the G11778 A mutation but without optic neuropathy were classified as unaffected carriers(n=22 eyes).Five family members(n=10 eyes)expressed the LHON phenotype and were classified as affected patients.Retinal images of all the subjects were taken by optical coherence tomography(OCT),and an automatic algorithm was used to segment the retina to eight layers.Horizontal and vertical OCT images centered on the fovea were used to measure intra-retinal layer thicknesses and foveal morphometry.RESULTS:Thicker foveal thickness,thinner foveal pit depth,and flatter foveal slopes were observed in unaffected carriers and affected LHON patients(all P<0.001).Further,the slopes of all four sectors in the LHON were flatter than those in the unaffected carriers(all P<0.001).Compared with the control group,affected LHON patients had a thinner retinal nerve fiber layer(RNFL),ganglion cell layer and inner plexiform layer(GCL+IPL),and total retina(all P<0.01).The retinal nerve fiber layer(RNFL)of affected patients was 38.0%thinner than that of controls while the GCL+IPL was 40.1%thinner.CONCLUSION:The foveal pit morphology shows changes in both unaffected carriers and affects patients.RNFL and GCL+IPL are thinner in affected LHON patients but not in unaffected carriers.展开更多
Objective： Leber＇s hereditary optic neuropathy （LHON） is a maternally inherited degeneration of the optic nerve caused by point mutations of mitochondrial DNA （mtDNA）. Many unsolved questions regarding the penet...Objective： Leber＇s hereditary optic neuropathy （LHON） is a maternally inherited degeneration of the optic nerve caused by point mutations of mitochondrial DNA （mtDNA）. Many unsolved questions regarding the penetrance and pathophysiological mechanism of LHON demand efficient and reliable mutation testing. This study aims to develop a minor groove binder （MGB） probe assay for rapid detection of mtDNA11778 mutation and heteroplasmy in Chinese LHON patients by real-time polymerase chain reaction （PCR）. Methods： Forty-eight patients suspected of having LHON and their maternal relatives underwent a molecular genetic evaluation, with 20 normal individuals as a control group at the same time. A real-time PCR involving two MGB probes was used to detect the mtDNA 1 1778 mutation and heteroplasmy. A linear standard curve was obtained by pUCmLHONG and pUCmLHONA clones. Results： All 48 LHON patients and their maternal relatives were positive for rntDNA11778 mutation in our assay, 27 heteroplasmic and 21 homoplasmic. Eighteen cases did not show an occurrence of the disease, while 9 developed the disease among the 27 heteroplasmic mutation cases. Eleven did not show an occurrence of the disease, while 10 cases developed the disease among 21 homoplasmic mutation cases. There was a significant difference in the incidence between the heteroplasmic and the homoplasmic mutation types. The time needed for running a real-time PCR assay was only 80 min. Conclusion： This real-time PCR assay is a rapid, reliable method for mtDNA mutation detection as well as heteroplasmy quantification. Detecting this ratio is very important for predicting phenotypic expression of unaffected carriers.展开更多
Purpose: To improve our diagnostic technique through the analysis of clinical features ofLeber's heredita'y optic neuropathy (LHON) harboring mtDNA point mutation at nt11778.Methods: Detection of nt11778 mutat...Purpose: To improve our diagnostic technique through the analysis of clinical features ofLeber's heredita'y optic neuropathy (LHON) harboring mtDNA point mutation at nt11778.Methods: Detection of nt11778 mutation was performed on 38 patients clinically diagnosed as LHON in our ophthalmic center from year 1998 to 2000. Circumstances of onset and family history were obtained and ophthalmoscopy, fundus fluorescein angiography, visual field and visual evoked potential were performed on all 38 patients. Result: 30 In 38 patients (78.95 % ) harbor nt11778 mutation, including 28 male (93.33%) and 2 female (6.67%). The ratio of affected male to female is 14: 1. Patients harboring nt11778 mutation display typical clinical nanifestations.Ccnclusion: Identification of one of the three LHON specifically associated ntDNA mutations is essential to confirm the diagnosis. Eye Science 2001: 17:31 ～ 34.展开更多
文摘AIM：To analyze the influences of different genotypes（G11778A,T14484 C and G3460A） of Leber hereditary optic neuropathy（LHON） on visual prognosis. METHODS： After a systematic literature search,all relevant studies evaluating the association between the three primary mutations of LHON and visual prognosis were included.All statistical tests were calculated with Revman 5.2 and STATA 12.0. RESULTS： Ten independent studies were included finally.A significant association between the three primary mutations and prognostic vision over 0.3 were found in G11778 A versus T14484 C [odds ratio（OR） =0.10,95% confidence interval（CI） =0.05-0.17,P 〈0.001],G11778 A versus G3460A（OR=0.18,95%CI=0.09-0.37,P 〈0.001） and T14484 C versus G3460A（OR =2.45,95% CI =1.10-5.48,P 〈0.05）.In addition,obtained by pairwise comparison,the vision during onset,age of onset and sex ratio of these three kinds of patients,have no statistical significance（P 〉0.05）.CONCLUSION： From pairwise comparison,we conclude that these three different genotypes of LHON are related to patients＇ visual prognosis.The T14484 C patients might have a best prognostic vision,G3460 A second,and G11778 A worst.And there is little relation between the three different genotypes and patients＇ vision,age of onset and sex ratio.
基金Supported by Wenzhou Technology Program(No.Y20160148).
文摘AIM:To investigate the foveal pit morphology changes in unaffected carriers and affected Leber’s hereditary optic neuropathy(LHON)patients with the G11778 A mutation from one family.METHODS:This study was a prospective cross-sectional study.Both eyes from 16 family members(age from 9 to 47 y)with the G11778 A mutation were analyzed and compared with 1 eye from 20 normal control subjects.Eleven family members with the G11778 A mutation but without optic neuropathy were classified as unaffected carriers(n=22 eyes).Five family members(n=10 eyes)expressed the LHON phenotype and were classified as affected patients.Retinal images of all the subjects were taken by optical coherence tomography(OCT),and an automatic algorithm was used to segment the retina to eight layers.Horizontal and vertical OCT images centered on the fovea were used to measure intra-retinal layer thicknesses and foveal morphometry.RESULTS:Thicker foveal thickness,thinner foveal pit depth,and flatter foveal slopes were observed in unaffected carriers and affected LHON patients(all P<0.001).Further,the slopes of all four sectors in the LHON were flatter than those in the unaffected carriers(all P<0.001).Compared with the control group,affected LHON patients had a thinner retinal nerve fiber layer(RNFL),ganglion cell layer and inner plexiform layer(GCL+IPL),and total retina(all P<0.01).The retinal nerve fiber layer(RNFL)of affected patients was 38.0%thinner than that of controls while the GCL+IPL was 40.1%thinner.CONCLUSION:The foveal pit morphology shows changes in both unaffected carriers and affects patients.RNFL and GCL+IPL are thinner in affected LHON patients but not in unaffected carriers.
基金the "Qianjiang Research Talent" grantfrom the Science and Technology Department of Zhejiang Province, China
文摘Objective： Leber＇s hereditary optic neuropathy （LHON） is a maternally inherited degeneration of the optic nerve caused by point mutations of mitochondrial DNA （mtDNA）. Many unsolved questions regarding the penetrance and pathophysiological mechanism of LHON demand efficient and reliable mutation testing. This study aims to develop a minor groove binder （MGB） probe assay for rapid detection of mtDNA11778 mutation and heteroplasmy in Chinese LHON patients by real-time polymerase chain reaction （PCR）. Methods： Forty-eight patients suspected of having LHON and their maternal relatives underwent a molecular genetic evaluation, with 20 normal individuals as a control group at the same time. A real-time PCR involving two MGB probes was used to detect the mtDNA 1 1778 mutation and heteroplasmy. A linear standard curve was obtained by pUCmLHONG and pUCmLHONA clones. Results： All 48 LHON patients and their maternal relatives were positive for rntDNA11778 mutation in our assay, 27 heteroplasmic and 21 homoplasmic. Eighteen cases did not show an occurrence of the disease, while 9 developed the disease among the 27 heteroplasmic mutation cases. Eleven did not show an occurrence of the disease, while 10 cases developed the disease among 21 homoplasmic mutation cases. There was a significant difference in the incidence between the heteroplasmic and the homoplasmic mutation types. The time needed for running a real-time PCR assay was only 80 min. Conclusion： This real-time PCR assay is a rapid, reliable method for mtDNA mutation detection as well as heteroplasmy quantification. Detecting this ratio is very important for predicting phenotypic expression of unaffected carriers.
文摘Purpose: To improve our diagnostic technique through the analysis of clinical features ofLeber's heredita'y optic neuropathy (LHON) harboring mtDNA point mutation at nt11778.Methods: Detection of nt11778 mutation was performed on 38 patients clinically diagnosed as LHON in our ophthalmic center from year 1998 to 2000. Circumstances of onset and family history were obtained and ophthalmoscopy, fundus fluorescein angiography, visual field and visual evoked potential were performed on all 38 patients. Result: 30 In 38 patients (78.95 % ) harbor nt11778 mutation, including 28 male (93.33%) and 2 female (6.67%). The ratio of affected male to female is 14: 1. Patients harboring nt11778 mutation display typical clinical nanifestations.Ccnclusion: Identification of one of the three LHON specifically associated ntDNA mutations is essential to confirm the diagnosis. Eye Science 2001: 17:31 ～ 34.
