1/51. Optic neuropathy in a patient with AIDS.We present a patient with acquired immunodeficiency syndrome (AIDS) with bilateral sequential optic neuropathies attributed to the 14484 mutation of Leber hereditary optic neuropathy (LHON). We discuss the potential interaction of the mitochondrial mutation with antiretroviral therapy and review the literature.- - - - - - - - - - ranking = 1keywords = optic (Clic here for more details about this article) |
2/51. Leber's hereditary optic neuropathy (LHON/11778) with myoclonus: report of two cases.The previously unrecognised association of myoclonus in two patients with LHON with the 11778/ND4 pathogenic mutation is described. EEG failed to disclose epileptic figures, and a back averaging study suggested that myoclonus was cortical in origin in both patients.- - - - - - - - - - ranking = 2keywords = optic (Clic here for more details about this article) |
3/51. Clinical, genetic, and biochemical characterization of a Leber hereditary optic neuropathy family containing both the 11778 and 14484 primary mutations.Four mitochondrial dna (mtDNA) mutations at nps 3460, 11778, 14484, and 14459 account for roughly 90% of cases of Leber hereditary optic neuropathy (LHON) and are designated as "primary" LHON mutations since they act as major predisposition factors for LHON. Although each primary mutation can arise independently on different mtDNA backgrounds during human evolution, they characteristically do not co-occur in LHON patients. We report here a family with the simultaneous occurrence of the 11778A and 14484C mutations. Neuro-ophthalmological examination of the proband, a nine-year-old Caucasian female, revealed the bilateral optic atrophy, central scotomas, and reduced visual acuity typical of LHON. Her mother had normal appearing optic discs and is today visually asymptomatic. Analysis of the proband blood mtDNA revealed that she harbored both the 11778A (heteroplasmic, 94% mutant) and the 14484C (homoplasmic mutant) mutation. This genotype was maintained in proband lymphoblasts and transmitochondrial cybrids. The mother also had both mutations, with the 14484C mutation homoplasmic in all cell types examined. However, only 31% of her blood mtDNAs carried the 11778 mutation, which segregated to essentially 100% wild-type in lymphoblast and cybrid mtDNA. Complex I-linked respiration and specific enzyme activity were consistently lowest in proband lymphoblast and cybrid mitochondria compared to those from the mother, 11778A patients, 14484C patients, or controls, thus demonstrating both a deleterious synergistic interaction between the 11778A and 14484C mutations and the magnitude of 11778A-associated complex I dysfunction. Remarkably, spontaneous vision recovery occurred in the proband, highlighting the complexities encountered when associating mtDNA genotype and complex I function with LHON expression.- - - - - - - - - - ranking = 4.3787964838397keywords = optic atrophy, optic, atrophy (Clic here for more details about this article) |
4/51. genetic counseling in Leber hereditary optic neuropathy (LHON).PURPOSE: To demonstrate the importance of mitochondrial dna (mtDNA) analysis in the diagnosis of Leber hereditary optic neuropathy (LHON) and illustrate the difficulties in genetic counseling of the disease. PARTICIPANTS AND methods: Ophthalmological and molecular genetic study of one affected and three unaffected members from a family with heteroplasmic ND1/3460 mtDNA mutation associated with LHON. RESULTS: The proband had variable amounts of mutant mtDNA in all his tissues studied, ranging from 58% in blood to 92% in subcutis. The mother had an extremely low amount of mutant mtDNA in her tissues, except for hair roots, which contained only normal mtDNA. No mutant mtDNA could be detected in the proband's unaffected sister and maternal aunt. CONCLUSIONS: Despite her minimal mutation load, the mother of the proband has still transmitted a considerable amount of mutant mtDNA to her son, who is severely affected. Although proband's unaffected sister and maternal aunt had no mutant mtDNA, a theoretical risk that they may transmit the disease to their offspring cannot be excluded.- - - - - - - - - - ranking = 2.5keywords = optic (Clic here for more details about this article) |
5/51. A mutational hot spot in the mitochondrial ND6 gene in patients with Leber's hereditary optic neuropathy.BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder characterized by rapid bilateral loss of central vision. Most patients harbor one of three mutations in the mitochondrial dna. In order to identify the genetic cause of the disease in one LHON patient without any of the three primary mutations, we sequenced the mitochondrial genome. methods: Ophthalmological examination was performed in the affected person and his unaffected relatives. The complete mitochondrial protein coding region was sequenced in the patient. RESULTS: Clinical examination of the affected 10-year-old Turkish boy showed typical features of LHON. Peripapillary microangiopathy was also seen in relatives of the maternal line. sequence analysis revealed a point mutation at position 14482 in the mitochondrial ND6 gene that changes a conserved methionine residue to isoleucine. A mutation at this nucleotide position has been previously suggested to be of pathogenic significance and has not been detected in any controls. CONCLUSIONS: We have identified that the mutation at nucleotide position 14482 which is the eight mutation in the ND6 gene that causes LHON, making this gene a hot spot for the disease. All eight identified mutations in the ND6 gene lie within the evolutionarily most conserved region of the ND6 gene in a hydrophobic pocket. This may help in understanding the pathomechanism of LHON.- - - - - - - - - - ranking = 2.5keywords = optic (Clic here for more details about this article) |
6/51. Leber's hereditary optic neuropathy with 3460 mitochondrial dna mutation.Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease causing acute or subacute, bilateral optic atrophy mainly in young men. It is found to be a mitochondrial disorder with the primary mitochondrial dna (mtDNA) mutations at 11,778, 3460, and 14,484. The incidence of each mutation is reported to be race-dependent. Point mutations at mtDNA nucleotide position 11,778 and 14,484 have been reported in Korean patients with LHON, however there has been no report of mtDNA mutation at nucleotide position 3460. Molecular genetic analyses at four primary sites (11,778, 14,484, 15,257, and 3460) of mitochondrial dna using the polymerase chain reaction, restriction enzyme digestion, and direct sequencing were performed in a 35-yr-old man with severe visual loss. A point mutation in the mtDNA at nucleotide position 3460 was identified and a conversion of a single alanine to a threonine was confirmed. To our knowledge, this is the first report confirming mtDNA mutation at nucleotide position 3460 in Korean patients with LHON. Detailed molecular analyses would be very helpful for the correct diagnosis of optic neuropathy of unknown etiology and for genetic counseling.- - - - - - - - - - ranking = 4.3787964838397keywords = optic atrophy, optic, atrophy (Clic here for more details about this article) |
7/51. White matter abnormalities in Leber's hereditary optic neuropathy due to the 3460 mitochondrial dna mutation.Leber's hereditary optic neuropathy is a maternally inherited disorder characterized by acute or subacute loss of central vision leading to severe optic atrophy. It is caused by mutations in the mitochondrial genome. Primary mutations are located at nucleotide positions 3460, 11778 and 14484 in genes encoding subunits of complex I of the respiratory chain. The occurrence of a demyelinating disease such as multiple sclerosis has been reported mainly in females with the 11778 mutation. We report a patient with Leber's hereditary optic neuropathy, kyphosis and white matter lesions in association with the 3460 mtDNA mutation. It is suggested that multiple sclerosis-like illness and deformities of the vertebral column may be associated pathogenically with Leber's hereditary optic neuropathy.- - - - - - - - - - ranking = 4.8787964838397keywords = optic atrophy, optic, atrophy (Clic here for more details about this article) |
8/51. phosphorus MR spectroscopy shows a tissue specific in vivo distribution of biochemical expression of the G3460A mutation in Leber's hereditary optic neuropathy.occipital lobe and calf muscle energy metabolism were studied in vivo by magnetic resonance spectroscopy (31P-MRS) in four members of a family harbouring the mitochondrial dna G3460A mutation causing Leber's hereditary optic neuropathy (LHON). Three siblings carried 100% mutated mitochondrial dna (homoplasmy), while their mother had coexistence of mutated and wild-type mitochondrial dna (heteroplasmy). Indices of brain energy metabolism on 31P-MRS were abnormal in all subjects examined, but the muscle oxidative phosphorylation rate was normal. These findings indicate a tissue specific distribution of the biochemical expression of the G3460A LHON mutation and suggest that extramitochondrial factors, such as nuclear genes, may influence expression of this mutation in vivo.- - - - - - - - - - ranking = 2.5keywords = optic (Clic here for more details about this article) |
9/51. Familial left ventricular hypertrabeculation in two blind brothers.So far, left ventricular hypertrabeculation (LVHT) has been described to occur only sporadically. In a 49-year-old man with Leber's hereditary optic neuropathy (LHON) due to the primary LHON mutation G3460A, arterial hypertension was reported since 2000 and palpitations since 1995. ECG revealed wolff-parkinson-white syndrome. Transthoracic echocardiography and cardiac MRI showed myocardial thickening and LVHT. pindolol markedly improved the cardiac abnormalities. Surprisingly, LVHT was also found in the 50-year-old brother of the index patient who also had LHON and also carried the G3460A mtDNA mutation. This brother also had wolff-parkinson-white syndrome and myocardial thickening, but without hypertension. It is concluded that LVHT, previously described to occur only sporadically, may be hereditary in single cases.- - - - - - - - - - ranking = 0.5keywords = optic (Clic here for more details about this article) |
10/51. Mitochondrial dna C4171A/ND1 is a novel primary causative mutation of Leber's hereditary optic neuropathy with a good prognosis.A novel mitochondrial dna C4171A mutation in the ND1 gene in two Korean families with Leber's hereditary optic neuropathy is described. All affected patients recovered spontaneously after suffering months to years of initial visual loss. This mutation replaces leucine with methionine in a conserved extramembrane loop of the ND1 gene and was absent in 514 normal controls and in 63 Leber's hereditary optic neuropathy lineages harboring the primary mutations. We consider mitochondrial dna C4171A/ND1 a primary causative mutation of Leber's hereditary optic neuropathy with a good prognosis.- - - - - - - - - - ranking = 3.5keywords = optic (Clic here for more details about this article) |
| | Next -> |