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
BACKGROUND This study aimed to explore clinical and molecular factors that cause discordance for clinical expression of Leber’s hereditary optic neuropathy(LHON)in a pair of identical twins with the 14484 point mutat...BACKGROUND This study aimed to explore clinical and molecular factors that cause discordance for clinical expression of Leber’s hereditary optic neuropathy(LHON)in a pair of identical twins with the 14484 point mutation.CASE SUMMARY Twin patients with the 14484 point mutation were studied for zygosity by using the Short Tandem Repeats Typing system.For the monozygotic twins,the radioactive restriction and densitometric analyses were used to quantitate the heteroplasmy level for the 14484 point mutation.The mitochondrial genome was analyzed to determine influential factors by mitochondrial deoxyribonucleic acid(DNA)sequencing,denaturing high-performance liquid chromatography and next generation sequencing.For the dizygotic twins,the nuclear DNA was analyzed.The twins with 14484 LHON were monozygotic with homoplasmy.No difference in the point mutation in mitochondrial DNA was found.No modifying genes that potentially influenced the disparity in phenotypic expression of LHON were detected in these twins.CONCLUSION This 11-year follow-up of monozygotic twins showed additional genetic modifications and epigenetic factors are possibly associated with discordance for LHON.展开更多
We amplified the 340 bp of mitochondrial DMA (mtDNA) by PCR including the recognized sequence of restriction enzyme of SfaN I . After amplification and digestion of SfaN I , two bands of 190 bp and 150 bp appeared in ...We amplified the 340 bp of mitochondrial DMA (mtDNA) by PCR including the recognized sequence of restriction enzyme of SfaN I . After amplification and digestion of SfaN I , two bands of 190 bp and 150 bp appeared in the mtDNA of four normal individuals but only one band of 340 bp appeared in the mtDNA with the mutation of G to A at the site of the nucleotide 11778 because such mutation destroyed the recognized sequence of SfaN I . We studied the mtDNAs of the patients with Leber's hereditary optic neur...展开更多
Inherited retinal degeneration is a major cause of incurable blindness characterized by loss of retinal photoreceptor cells.Inherited retinal degeneration is characterized by high genetic and phenotypic heterogeneity ...Inherited retinal degeneration is a major cause of incurable blindness characterized by loss of retinal photoreceptor cells.Inherited retinal degeneration is characterized by high genetic and phenotypic heterogeneity with several genes mutated in patients affected by these genetic diseases.The high genetic heterogeneity of these diseases hampers the development of effective therapeutic interventions for the cure of a large cohort of patients.Common cell demise mechanisms can be envisioned as targets to treat patients regardless the specific mutation.One of these targets is the increase of intracellular calcium ions,that has been detected in several murine models of inherited retinal degeneration.Recently,neurotrophic factors that favor the efflux of calcium ions to concentrations below toxic levels have been identified as promising molecules that should be evaluated as new treatments for retinal degeneration.Here,we discuss therapeutic options for inherited retinal degeneration and we will focus on neuroprotective approaches,such as the neuroprotective activity of the Pigment epithelium-derived factor.The characterization of specific targets for neuroprotection opens new perspectives together with many questions that require deep analyses to take advantage of this knowledge and develop new therapeutic approaches.We believe that minimizing cell demise by neuroprotection may represent a promising treatment strategy for retinal degeneration.展开更多
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Supported by the Faculty of Medicine Siriraj Hospital,Mahidol University,No.(IO)R015731040。
文摘BACKGROUND This study aimed to explore clinical and molecular factors that cause discordance for clinical expression of Leber’s hereditary optic neuropathy(LHON)in a pair of identical twins with the 14484 point mutation.CASE SUMMARY Twin patients with the 14484 point mutation were studied for zygosity by using the Short Tandem Repeats Typing system.For the monozygotic twins,the radioactive restriction and densitometric analyses were used to quantitate the heteroplasmy level for the 14484 point mutation.The mitochondrial genome was analyzed to determine influential factors by mitochondrial deoxyribonucleic acid(DNA)sequencing,denaturing high-performance liquid chromatography and next generation sequencing.For the dizygotic twins,the nuclear DNA was analyzed.The twins with 14484 LHON were monozygotic with homoplasmy.No difference in the point mutation in mitochondrial DNA was found.No modifying genes that potentially influenced the disparity in phenotypic expression of LHON were detected in these twins.CONCLUSION This 11-year follow-up of monozygotic twins showed additional genetic modifications and epigenetic factors are possibly associated with discordance for LHON.
文摘We amplified the 340 bp of mitochondrial DMA (mtDNA) by PCR including the recognized sequence of restriction enzyme of SfaN I . After amplification and digestion of SfaN I , two bands of 190 bp and 150 bp appeared in the mtDNA of four normal individuals but only one band of 340 bp appeared in the mtDNA with the mutation of G to A at the site of the nucleotide 11778 because such mutation destroyed the recognized sequence of SfaN I . We studied the mtDNAs of the patients with Leber's hereditary optic neur...
基金supported by grants from the Telethon Foundation(GGP14180,GGP19113)the European Union(LSHGCT-2005-512036 and transMed,MSCA-ITN-2017-765441)(all to VM)
文摘Inherited retinal degeneration is a major cause of incurable blindness characterized by loss of retinal photoreceptor cells.Inherited retinal degeneration is characterized by high genetic and phenotypic heterogeneity with several genes mutated in patients affected by these genetic diseases.The high genetic heterogeneity of these diseases hampers the development of effective therapeutic interventions for the cure of a large cohort of patients.Common cell demise mechanisms can be envisioned as targets to treat patients regardless the specific mutation.One of these targets is the increase of intracellular calcium ions,that has been detected in several murine models of inherited retinal degeneration.Recently,neurotrophic factors that favor the efflux of calcium ions to concentrations below toxic levels have been identified as promising molecules that should be evaluated as new treatments for retinal degeneration.Here,we discuss therapeutic options for inherited retinal degeneration and we will focus on neuroprotective approaches,such as the neuroprotective activity of the Pigment epithelium-derived factor.The characterization of specific targets for neuroprotection opens new perspectives together with many questions that require deep analyses to take advantage of this knowledge and develop new therapeutic approaches.We believe that minimizing cell demise by neuroprotection may represent a promising treatment strategy for retinal degeneration.
