GENETICS OF HEREDITARY ATAXIA WITH MACULAR DEGENERATION

橄榄桥小脑萎缩(OPCA)是一组异质性的人类 影响下小脑橄榄核的神经退行性疾病 核团和脑桥。基因连锁已经确定了两个不同的OPCA 6P和12Q染色体上的基因座。一些看似典型的OPCA家系 是根据黄斑变性的存在来区分的 最终导致失明。OPCA和黄斑病变的家系 退化表示预期，增加的现象 连续几代疾病的严重性和更早的疾病发病 家人。OPCA合并黄斑病变(OPCA+M)的基因是遗传的 与以前的两个本地化形式不同，因为它不映射到 染色体6p或12q。这项建议旨在实现本地化和 导致这种疾病的基因的特征。我们已经确定了 四个患有OPCA+M的大家庭使这一目标成为可能。我们有 已经进行了临床评估并从这些患者中抽取了57人 家人。突出的预期和视网膜受累是独一无二的 可能在这项工作中提供重要线索的特征。 对疾病基因的鉴定将有助于更好地理解 与这种疾病有关的退化过程。它将铺平 对大脑和视网膜细胞退化的新见解 也可能解释对所看到的预期的遗传解释 在这些家庭里。

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.