GENETICS OF HEREDITARY ATAXIA WITH MACULAR DEGENERATION

橄榄桥脑小脑萎缩（OPCA）是一种异质性的人类 影响小脑下橄榄核的神经变性疾病 核和脑桥。遗传连锁已经确定了两个不同的OPCA 染色体6p和12q上的基因座。一些家庭与看似典型的OPCA 是基于黄斑变性的存在而区分的， 最终导致失明。 OPCA和黄斑的家族 退化表现出预期，增加的现象， 在连续几代疾病中， 家庭 OPCA与黄斑病变（OPCA+ M）的基因是遗传性的， 与之前的两种本地化形式不同，因为它不映射到 染色体6p或12q。 这项建议旨在本地化， 这是对导致这种疾病的基因的描述。我们已经确定 OPCA+ M的四个大家族使这一目标变得可行。我们有 已经对57名患者进行了临床评估和采样， 家庭突出的预期和视网膜受累是独特的 这些特征可能为这项工作提供重要线索。 疾病基因的鉴定将有助于更好地了解 与这种疾病有关的退化过程。它将铺平道路 一种新的方式来了解大脑和视网膜的细胞变性 也可能阐明遗传学对所见预期的解释 在这些家庭中。

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.