1/46. Mapping and genomic characterization of the gene encoding diacylglycerol kinase gamma (DAGK3): assessment of its role in dominant optic atrophy (OPA1).The family of diacylglycerol kinases (DAGKs) is known to play an important role in signal transduction linked to phospholipid turnover. In the fruitfly drosophila melanogaster, a human DAGK ortholog, DGK2, was shown to underlie the phenotype of the visual mutant retinal degeneration A (rdgA). Previously, the gene encoding a novel member of the human DAGK family, termed DAGK3, was cloned and demonstrated to be abundantly expressed in the human retina. Based on these findings we reasoned that DAGK3 might be an excellent candidate gene for a human eye disease. In the present study, we report the genomic organization of the human DAGK3 gene, which spans over 30 kb of genomic dna interrupted by 23 introns. In addition, we have mapped the gene locus by fluorescence in situ hybridization to 3q27-28, overlapping the chromosomal region known to contain the gene underlying dominant optic atrophy (OPA1), the most common form of hereditary atrophy of the optic nerve. Mutational analysis of the entire coding region of DAGK3 in 19 unrelated German OPA1 patients has not revealed any disease-causing mutations, therefore excluding DAGK3 as a major cause underlying OPA1.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
2/46. Leber's hereditary optic neuropathy (LHON) with mitochondrial ND4 gene mutation (11778) in a Thai patient.Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease, characterized by bilateral optic atrophy predominantly in healthy young males. This disorder has shown to be associated with dna mutation in mitochondrial genome of the patients. We report here a young man who came to the hospital with subacute visual loss in one eye, followed by the other eye within two months. His echocardiogram was normal. A G-->A base substitution at nucleotide position 11,778 which changes a conserved arginine to histidine at amino acid position 340 of ND4, a protein subunit of respiratory chain enzyme complex I in oxidative phosphorylation system, was detected in his leucocyte mitochondrial genome.- - - - - - - - - - ranking = 0.16666666666667keywords = atrophy (Clic here for more details about this article) |
3/46. Choreic movements and MRI abnormalities in the subthalamic nuclei reversible after administration of coenzyme Q10 and multiple vitamins in a patient with bilateral optic neuropathy.A 37-year-old man developed choreic movements of the limbs over a few months. His medical history included bilateral visual loss detected at the age of 9 and worsening at age 20. Visual field testing showed a central scotoma. Fundus examination showed atrophy of the optic disks and narrowing of vessels. The diagnosis of Leber hereditary optic neuropathy (LHON) was considered. There was no family history of visual loss or movement disorders. blood lactate:pyruvate ratio was moderately elevated. Skeletal muscle biopsy was normal. magnetic resonance imaging showed bilateral hypointense lesions on T1-weighted sequences in the subthalamic nuclei and in the lateral part of the substantia nigra. Linear hyperlucencies in the pyramidal tract facing the lateral part of the ruber nuclei were also demonstrated on T2-weighted sequences. Nine LHON-associated mutations were ruled out by RFLP analysis. Treatment with 250 mg coenzyme Q10 per day and multiple vitamins was initiated. Gradual recovery in movement disorders occurred over 1 year. Lactate to pyruvate ratio normalized. No change of visual function was observed. On magnetic resonance imaging performed 3 years later, lesions of the subthalamic nuclei almost completely disappeared. We think the patient might have an unusual, genetically uncharacterized mitochondrial disorder, combining optic neuropathy and chorea.- - - - - - - - - - ranking = 0.16666666666667keywords = atrophy (Clic here for more details about this article) |
4/46. Mitochondrial dna mutation at np 3243 in a family with maternally inherited diabetes mellitus.Mitochondrial dna (mtDNA) gene defects may play a role in the development of maternally inherited diabetes mellitus and deafness (MIDD). A family from Southern italy who showed maternal transmission of type 2 diabetes mellitus with three individuals affected is described. A 10.4 kb deletion and mutations at nucleotide positions (np) 3243, 7445 and 11778 in the mtDNA of six relatives were sought. The mitochondrial np 3243 mutation of the tRNA Leu (UUR) gene was identified in a boy affected by optic atrophy and mental retardation, as well as in his diabetic mother. No other mutations or deletions were found. Our study points out the variable phenotypic expression of the np 3243 mtDNA mutation. This may suggest the presence of other mitochondrial or nuclear mutations required to modulate the phenotype. A clinical and metabolic follow-up of all family members was necessary to understand the role of the np 3243 mutation, especially in one child affected by optic atrophy and mental retardation. Further studies will be aimed at investigating the prevalence of mutations and deletions of mtDNA in type 2 diabetes mellitus.- - - - - - - - - - ranking = 0.33333333333333keywords = atrophy (Clic here for more details about this article) |
5/46. A family with Leber's hereditary optic neuropathy with mitochondrial 11778/ND4 and 4216/ND1 mutations.Leber's hereditary optic neuropathy (LHON) is caused by a point mutation in the mitochondrial deoxynucleic acid (mtDNA) and accounts for 30% of bilateral optic atrophy of unknown etiology. The authors found a Korean family with mtDNA mutations in the nucleotide positions (np) 11778 and np 4216. This is the first report confirming a secondary mtDNA np 4216 mutation in Koreans, as well as the first report of a Korean family harboring both primary and the secondary mutations that the authors are aware of.- - - - - - - - - - ranking = 0.16666666666667keywords = atrophy (Clic here for more details about this article) |
6/46. The luminance fall in anomaloscope examination: clinical examples.PURPOSE: The evaluation of the anomaloscope slope quotient in patients with acquired colour vision deficiency. methods: Two patients with Stargardt's disease in combination with protanomaly and deuteranomaly, respectively, were selected and also 3 patients with a presumed dominant optic atrophy of the protan type. The anomaloscope examination was performed according to the Linksz procedure. The luminance fall was calculated as the slope quotient SQ:Y units luminance fall per X units width of the matching range. RESULTS: The SQ of the 2 Stargardt patients was steeper than the SQ of congenital colour vision defectives, especially at the red end of the anomaloscope green-red mixture scale, indicating pathologic scotopization superimposed on the congenital deficiency. In optic atrophy of the protan type the SQ was flatter than in congenital deficiency, indicating that this deficiency has nothing to do with congenital protan deficiency. CONCLUSION: Calculation of the slope quotient SQ is helpful for the diagnosis of acquired colour vision deficiency, especially when the subject also has a congenital colour vision deficiency or is supposed to have such a deficiency.- - - - - - - - - - ranking = 0.33333333333333keywords = atrophy (Clic here for more details about this article) |
7/46. Novel mutation in RP2 gene in two brothers with X-linked retinitis pigmentosa and mtDNA mutation of leber hereditary optic neuropathy who showed marked differences in clinical severity.PURPOSE: To report the identification of a novel mutation of the RP2 gene in two Japanese brothers with X-linked retinitis pigmentosa of a differing clinical severity. The mother was a carrier of both retinitis pigmentosa and optic atrophy. methods: The older brother had a severe form of retinitis pigmentosa associated with macular degeneration and total optic atrophy, whereas the younger brother presented typical X-linked retinitis pigmentosa. RESULTS: Each patient exhibited a novel 2-bp insertion at codon 278 in exon 3 of the RP2 gene as well as a 11778 mutation in mitochondrial dna. This suggests that the older brother may have developed Leber hereditary optic neuropathy as well as retinitis pigmentosa. CONCLUSION: Molecular testing confirmed the clinical diagnosis in each case. However, such testing did not explain the differences in the severity of the ophthalmoscopic findings between the two brothers.- - - - - - - - - - ranking = 0.33333333333333keywords = atrophy (Clic here for more details about this article) |
8/46. Four siblings with Hallervorden-Spatz disease.We reported four cases of Hallervorden-Spatz disease. All four siblings (three males and one female) in the family are affected. The first symptoms of the disease were spastic paraparesis and optic atrophy followed by trunkal dystonia and lower motor neurone involvement. The average age of the onset was 4.25 years. The diagnosis was made at the ages of 17, 14, 11 and 10 years. The diagnosis was confirmed clinically, electrophysiologically and by MRI. On MRI scans all patients demonstrated hypointense areas in globus pallidus. There is neither specific treatment nor prenatal diagnosis.- - - - - - - - - - ranking = 0.16666666666667keywords = atrophy (Clic here for more details about this article) |
9/46. Disc excavation in dominant optic atrophy: differentiation from normal tension glaucoma.OBJECTIVE: In patients with dominant optic atrophy (DOA, Kjer type), excavation of the optic nerve develops, and these patients may be misdiagnosed as having normal tension glaucoma (NTG). This study examined disc morphologic features in patients with DOA and explored features that help distinguish this condition from NTG. DESIGN: Noncomparative, observational case series. PARTICIPANTS: patients with DOA who were seen at the Duke University eye Center between 1987 and 1996 and who had bilateral optic nerve photographs. methods: Retrospective chart review of the results of visual acuity testing, visual field testing by Goldmann perimetry, color vision testing, intraocular pressure measurement, and observation of bilateral optic nerve photographs. MAIN OUTCOME MEASURES: Appearance of the optic disc and peripapillary zone in patients with DOA. RESULTS: Nine patients were identified. The mean age at the time of evaluation was 28 years (range, 11-62 years). Most patients had a mild to moderate reduction in visual acuity. color vision as tested with Hardy-Rand-Rittler plates was reduced (4.0/10 /- 4.2/10). A cup-to-disc ratio of more than 0.5 was observed in at least one eye of eight patients. A temporal wedge-shaped area of excavation was observed in 14 of the 18 eyes studied. Moderate to severe temporal pallor was observed in all of the eyes. pallor of the remaining (noncupped) neuroretinal rim was also observed consistently, ranging from mild to moderate. A gray crescent and some degree of peripapillary atrophy were noted in all eyes. CONCLUSIONS: Several clinical features, including early age of onset, preferential loss of central vision, sparing of the peripheral fields, pallor of the remaining neuroretinal rim, and a family history of unexplained visual loss or optic atrophy, help to distinguish patients with DOA from those with NTG.- - - - - - - - - - ranking = 1.1666666666667keywords = atrophy (Clic here for more details about this article) |
10/46. Two cases of hereditary optic atrophy associated with an enzymatic defect of the respiratory chain.Hereditary optic atrophy is a significant cause of optic atrophy in children. We report two male siblings who suffered profound irreversible loss of vision over a 2-month period. Neither patient had any prior ophthalmic problems. Both siblings had a metabolic disorder characterized by transient episodes of ataxia and paresis, whereas in one brother a slight increase of lactate in blood and cerebrospinal fluid was detected during an acute episode. Respiratory chain defect in complex I was confirmed in one patient.- - - - - - - - - - ranking = 1keywords = atrophy (Clic here for more details about this article) |
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