GENETICS OF HEREDITARY ATAXIA WITH MACULAR DEGENERATION

点击翻译按钮获取中文摘要

Olivopontocerebellar atrophy (OPCA) is a heterogeneous group of human neurodegenerative diseases affecting the inferior cerebellum, olivary nuclei, and the pons. Genetic linkage has identified two distinct OPCA loci on chromosomes 6p and 12q. Some families with seemingly typical OPCA are distinguished based on the presence of macular degeneration that ultimately leads to blindness. The families with OPCA and macular degeneration demonstrate anticipation, the phenomenon of increasing severity and earlier disease onset in successive generations of disease families. The gene for OPCA with maculopathy (OPCA+ M) is genetically distinct from the two previously localized forms as it does not map to either chromosome 6p or 12q. This proposal is aimed at localization and characterization of the gene causing this disorder. We have identified four large families with OPCA+ M that make this goal feasible. We have already clinically evaluated and sampled 57 individuals from these families. The prominent anticipation and retinal involvement are unique features that may provide important clues in this undertaking. Identification of the disease gene will lead to better understanding of the degenerative processes associated with this disease. It will pave the way for new insights into cellular degeneration of the brain and retina and may also elucidate the genetic explanation for the anticipation seen in these families.