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.