To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomog raphy (OCT) in unaffected carriers with Leber’s hereditary optic neuropathy (LH ON) mutations. Crosssectional study. Sixty-six unaffected...To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomog raphy (OCT) in unaffected carriers with Leber’s hereditary optic neuropathy (LH ON) mutations. Crosssectional study. Sixty-six unaffected carriers (44 females and 22 males) were analyzed and compared with an age-matched control group of 7 0 patients (40 females and 30 males). The statistical analysis was performed aft er grouping both the patients and the control group on the basis of gender and, for unaffected carriers only, mitochondrial DNA mutation. The Fast RNFL Thicknes s (3.4) scan acquisition protocol was used. Retinal nerve fiber layer thickness as measured by OCT. With respect to the control group, unaffected male carriers showed a thicker RNFL in the temporal and inferior quadrants and in the 360°ave rage measurement (P=0.025, P=0.03, and P=0.018, respectively). These differences reached statistical significance in subjects carrying the 11 778 mutation, wher eas only a trend was detected in those with the 3 460 mutation. Unaffected femal e carriers had an increased thickness in the temporal quadrant when compared wit h the control group (P=0.003) and no differences in the other measurements. The increase in temporal sectors was statistically significant in females with the 1 1 778 mutation, whereas a trend was detected in those with the 3 460 mutation. A thickening of the temporal fibers was detected in all subgroups of unaffected c arriers. This is the first evidence indicating the preferential involvement of t he papillomacular bundle in subclinical LHON. This notion previously was based o n the early loss of fibers from the temporal quadrant in acute LHON and the sele ctive loss of small-caliber fibers at histopathology. Our study also revealed t hat males have a more diffuse involvement than females.展开更多
To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomog raphy (StratusOCT) in patients with Leber’s hereditary optic neuropathy (LHON). Cross-sectional study. Thirty-eight patients with LHON we...To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomog raphy (StratusOCT) in patients with Leber’s hereditary optic neuropathy (LHON). Cross-sectional study. Thirty-eight patients with LHON were analyzed and comp ared with an age-matched control group of 75 patients. Patients with LHON were classified as having early LHON (E-LHON, n=8) when the duration of the disease was shorter than 6 months and atrophic LHON (A-LHON, n=30) when the duration wa s longer than 6 months. The fast RNFL thickness (3.4) scan acquisition protocol was used. Retinal nerve fiber layer thickness as measured by StratusOCT. Compare d with the control group, eyes with E-LHON showed a thicker RNFL in the 360°av erage measurement (P < 0.01) and in the superior (P < 0.01), nasal (P < 0.05), a nd inferior quadrants (P < 0.05); no significant changes were detected in the te mporal quadrant. Eyes with A-LHON revealed a thinner RNFL in all measurements ( P < 0.001); the fibers of the nasal quadrant showed the lowest amount of reducti on (38%vs. 42%-49.8%in the other quadrants). In cases with A-LHON and visual recovery, RNFL was significantly thicker in all measur ements (P < 0.001), except the temporal quadrant, with respect to A-LHON withou t visual recovery. On the basis of OCT data, the RNFL is thickened in E-LHON an d severely thinned in A-LHON. RNFL is likely to be partially preserved in A-LH ON with visual recovery. The temporal fibers (papillomacular bundle) are the fir st and most severely affected; the nasal fibers seem to be partially spared in t he late stage of the disease.展开更多
A novel mitochondrial DNA (mtDNA) transition (3733G→ A) inducing the E143 K amino acid change at a very conserved site of the NADH dehydrogenase subunit 1 (ND1) was identified in a family with six maternally related ...A novel mitochondrial DNA (mtDNA) transition (3733G→ A) inducing the E143 K amino acid change at a very conserved site of the NADH dehydrogenase subunit 1 (ND1) was identified in a family with six maternally related individuals with Leber’ s hereditary optic neuropathy (LHON) and in an unrelated sporadic case, all negative for known mutations and presenting with the canonical phenotype. The transition was not detected in 1,082 control mtDNAs and was heteroplasmic in several individuals from both pedigrees. In addition, the mtDNAs of the two families were found to belong to different haplogroups (H and X), thus confirming that the 3733G→ A mutation occurred twice independently. Phosphorus magnetic resonance spectroscopy disclosed an in vivo brain and skeletal muscle energy metabolism deficit in the four examined patients. Muscle biopsy from two patients showed slight mitochondrial proliferation with abnormal mitochondria. Biochemical investigations in platelets showed partially insensitive complex I to rotenone inhibition. We conclude that the 3733G→ A transition is a novel cause of LHON and, after those at positions 3460 and 4171, is the third ND1 mutation to be identified in multiple unrelated families. This finding shows that, in addition to ND6, the ND1 subunit gene is also a mutational hot spot for LHON.展开更多
文摘To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomog raphy (OCT) in unaffected carriers with Leber’s hereditary optic neuropathy (LH ON) mutations. Crosssectional study. Sixty-six unaffected carriers (44 females and 22 males) were analyzed and compared with an age-matched control group of 7 0 patients (40 females and 30 males). The statistical analysis was performed aft er grouping both the patients and the control group on the basis of gender and, for unaffected carriers only, mitochondrial DNA mutation. The Fast RNFL Thicknes s (3.4) scan acquisition protocol was used. Retinal nerve fiber layer thickness as measured by OCT. With respect to the control group, unaffected male carriers showed a thicker RNFL in the temporal and inferior quadrants and in the 360°ave rage measurement (P=0.025, P=0.03, and P=0.018, respectively). These differences reached statistical significance in subjects carrying the 11 778 mutation, wher eas only a trend was detected in those with the 3 460 mutation. Unaffected femal e carriers had an increased thickness in the temporal quadrant when compared wit h the control group (P=0.003) and no differences in the other measurements. The increase in temporal sectors was statistically significant in females with the 1 1 778 mutation, whereas a trend was detected in those with the 3 460 mutation. A thickening of the temporal fibers was detected in all subgroups of unaffected c arriers. This is the first evidence indicating the preferential involvement of t he papillomacular bundle in subclinical LHON. This notion previously was based o n the early loss of fibers from the temporal quadrant in acute LHON and the sele ctive loss of small-caliber fibers at histopathology. Our study also revealed t hat males have a more diffuse involvement than females.
文摘To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomog raphy (StratusOCT) in patients with Leber’s hereditary optic neuropathy (LHON). Cross-sectional study. Thirty-eight patients with LHON were analyzed and comp ared with an age-matched control group of 75 patients. Patients with LHON were classified as having early LHON (E-LHON, n=8) when the duration of the disease was shorter than 6 months and atrophic LHON (A-LHON, n=30) when the duration wa s longer than 6 months. The fast RNFL thickness (3.4) scan acquisition protocol was used. Retinal nerve fiber layer thickness as measured by StratusOCT. Compare d with the control group, eyes with E-LHON showed a thicker RNFL in the 360°av erage measurement (P < 0.01) and in the superior (P < 0.01), nasal (P < 0.05), a nd inferior quadrants (P < 0.05); no significant changes were detected in the te mporal quadrant. Eyes with A-LHON revealed a thinner RNFL in all measurements ( P < 0.001); the fibers of the nasal quadrant showed the lowest amount of reducti on (38%vs. 42%-49.8%in the other quadrants). In cases with A-LHON and visual recovery, RNFL was significantly thicker in all measur ements (P < 0.001), except the temporal quadrant, with respect to A-LHON withou t visual recovery. On the basis of OCT data, the RNFL is thickened in E-LHON an d severely thinned in A-LHON. RNFL is likely to be partially preserved in A-LH ON with visual recovery. The temporal fibers (papillomacular bundle) are the fir st and most severely affected; the nasal fibers seem to be partially spared in t he late stage of the disease.
文摘A novel mitochondrial DNA (mtDNA) transition (3733G→ A) inducing the E143 K amino acid change at a very conserved site of the NADH dehydrogenase subunit 1 (ND1) was identified in a family with six maternally related individuals with Leber’ s hereditary optic neuropathy (LHON) and in an unrelated sporadic case, all negative for known mutations and presenting with the canonical phenotype. The transition was not detected in 1,082 control mtDNAs and was heteroplasmic in several individuals from both pedigrees. In addition, the mtDNAs of the two families were found to belong to different haplogroups (H and X), thus confirming that the 3733G→ A mutation occurred twice independently. Phosphorus magnetic resonance spectroscopy disclosed an in vivo brain and skeletal muscle energy metabolism deficit in the four examined patients. Muscle biopsy from two patients showed slight mitochondrial proliferation with abnormal mitochondria. Biochemical investigations in platelets showed partially insensitive complex I to rotenone inhibition. We conclude that the 3733G→ A transition is a novel cause of LHON and, after those at positions 3460 and 4171, is the third ND1 mutation to be identified in multiple unrelated families. This finding shows that, in addition to ND6, the ND1 subunit gene is also a mutational hot spot for LHON.
