1/7. Progressive autosomal dominant optic atrophy and sensorineural hearing loss in a Turkish family.PURPOSE: To describe the clinical features, mode of inheritance, and linkage analysis of ten affected members of a three-generation family with progressive optic atrophy and progressive hearing loss. MATERIALS AND methods: The proband, a 10-year-old boy, presented with progressive visual failure. Ten other members in his family, including his mother, half-sister, aunt, two uncles, grandfather, and some of the cousins, also had progressive visual loss and hearing loss. Six affected and four unaffected cases were examined in detail. blood samples were drawn from 16 members for dna extraction. Two loci previously described for optic atrophy were tested for linkage in the present family. RESULTS: The mode of inheritance was clearly autosomal dominant. Six members of the family were found to have progressive optic atrophy and hearing loss, both starting in the first decade of life. Total or red-green color blindness was detected in some patients. None of the members of this family showed evidence of other systemic disorders; however, four had blepharochalasis. No other cause could be found for the hearing or the visual loss. Linkage analysis excluded OPA1 and OPA2. CONCLUSION: The present Turkish family belongs to the group of individuals with autosomal dominantly inherited optic atrophies with hearing loss. Linkage analysis excluded OPA1 and OPA2, indicating that a novel gene defect underlies the disease in this family. Further genome-wide linkage analysis and identification of the disease-associated gene will help define the pathophysiology of this syndrome. ( info) |
2/7. Hereditary motor and sensory neuropathy type VI with optic atrophy.PURPOSE: To present the detailed clinical findings of a large family with hereditary motor and sensory neuropathy type VI (HMSN VI), a syndrome featuring optic atrophy. DESIGN: Observational case series. methods: A detailed history was obtained and physical examination was made of the extended family of the proband for evidence of neurologic dysfunction. The OPA1 gene was screened for mutations by direct dna sequencing. RESULTS: Twelve of 97 family members examined are affected with signs of HMSN VI. Three other members have either optic atrophy or peripheral neuropathy, thus allowing an appreciation of the full clinical spectrum of disease. No mutations were found in the OPA1 gene. CONCLUSIONS: This family demonstrates the variable expressivity of this disorder as well as incomplete penetrance. This is the largest known family with HMSN VI. No association was found with changes in the OPA1 gene. ( info) |
3/7. Unexplained visual loss.Dominant optic atrophy is the most common heredodegenerative optic neuropathy. Typically, patients present with slowly progressive, bilaterally decreased central visual acuity. Subtle central or cecocentral visual field defect and normal peripheral isopters are demonstrated with perimetry. A defect in blue-yellow discrimination (tritan error axis) is the most common type of dyschromatopsia, however protan and deutan axes may be superimposed. A characteristic optic disk appearance includes temporal disk pallor with excavation. An autosomal dominant inheritance pattern can often be elicited from the family history. ( info) |
4/7. The association of autosomal dominant optic atrophy and moderate deafness may be due to the R445H mutation in the OPA1 gene.PURPOSE: To examine the involvement of the optic atrophy 1 (OPA1) gene in optic atrophy associated with moderate deafness. DESIGN: Observational case report.The entire coding sequence of the OPA1 gene was directly sequenced in the case of a patient suffering from optic atrophy associated with moderate deafness. RESULTS: A de novo heterozygous mutation R445H in the OPA1 gene was found. No similar mutation was detected in either of the patient's parents or in the 100 chromosome controls. CONCLUSION: The R445H mutation in OPA1 might be the cause of the association between dominant optic atrophy and moderate deafness, a phenotype that may be currently underdiagnosed. ( info) |
5/7. Short wavelength-automated perimetry compared with standard achromatic perimetry in autosomal dominant optic atrophy.BACKGROUND: Autosomal dominant optic atrophy (ADOA, Kjer-type) is a heterogeneous, non-inflammatory degeneration of retinal ganglion cells. The diagnosis of ADOA can be challenging owing to its insidious onset and large variability in phenotypic expression, both within and between individual pedigrees. The earliest literature reports relatively mild centrocaecal scatomas to white targets in ADOA, but extensive and dense peripheral field loss to coloured targets, especially blue, with Bjerrum perimetry. The phrase "inverted peripheral visual fields to coloured targets" has been used to describe this phenomenon. methods: Humphrey standard achromatic perimetry (SAP) and short wavelength-automated perimetry (SWAP) were carried out on five patients with ADOA. RESULTS: Regardless of wide variations in patient age, visual acuity, disc appearance and colour vision, the SWAP mean deviation (MD) was between 10 and 20 times more depressed than the SAP MD. The actual differences ranged from 9.38 to 13.78 dB. CONCLUSIONS: These data are consistent with the original reports suggesting that, early in this disease process, the blue-target deficits are typically peripheral and that this difference between SAP and SWAP perimetry may be a robust indicator of ADOA in both early and late stages of this disease. ( info) |
6/7. A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4-Xp11.2.Autosomal dominant optic atrophy (ADOA) is the most common inherited optic atrophy. Clinical features of ADOA include a slowly progressive bilateral loss of visual acuity, constriction of peripheral visual fields, central scotomas, and color vision abnormalities. Although ADOA is the most commonly inherited optic atrophy, autosomal recessive, X-linked, mitochondrial, and sporadic forms have also been reported. Four families with X-linked optic atrophy (XLOA) were previously described. One family was subsequently linked to Xp11.4-Xp11.2 (OPA2). This investigation studied one multi-generation family with an apparently X-linked form of optic atrophy and compared their clinical characteristics with those of the previously described families, and determined whether this family was linked to the same genetic locus. Fifteen individuals in a three-generation idaho family underwent complete eye examination, color vision testing, automated perimetry, and fundus photography. Polymorphic markers were used to genotype each individual and to determine linkage. Visual acuities ranged from 20/30 to 20/100. All affected subjects had significant optic nerve pallor. Obligate female carriers were clinically unaffected. Preliminary linkage analysis (lod score = 1.8) revealed that the disease gene localized to the OPA2 locus on Xp11.4-Xp11.2. Four forms of inherited optic neuropathy, ADOA, autosomal recessive optic atrophy (Costeff syndrome), Leber hereditary optic neuropathy, and charcot-marie-tooth disease with optic atrophy, are associated with mitochondrial dysfunction. Future identification of the XLOA gene will reveal whether this form of optic atrophy is also associated with a mitochondrial defect. Identification of the XLOA gene will advance our understanding of the inherited optic neuropathies and perhaps suggest treatments for these diseases. An improved understanding of inherited optic neuropathies may in turn advance our understanding of acquired optic nerve diseases, such as glaucoma and ischemic optic neuropathy. ( info) |
7/7. Prognostic dna testing and counselling for dominant optic atrophy due to a novel OPA1 mutation.CASE REPORT: To report the case of a 26-year-old woman with a family history of dominant optic atrophy who requested dna testing and counselling. Ophthalmologic examination showed her affected father had bilateral temporal papillary pallor. Direct genomic sequencing of the OPA1 gene revealed a novel heterozygous nonsense mutation (Arg879stop). Because no mutation in OPA1 was detected in the daughter, we could counsel her that the possibility was very low that she was a carrier or would pass the disease-causing gene to her children. COMMENTS: Our study provides evidence of the apparent value of molecular genetic analysis of OPA1 gene as predictive dna testing, although the exact risk and benefit of this type of analysis awaits further study. ( info) |