Clinical and Genetic studies of autosomal dominant cerebellar ataxia (Miyakonojo type)

常染色体显性遗传性小脑共济失调（ADCA）是一组临床和遗传异质性疾病。尽管存在表型差异，SCA 4和日本16 q连锁ADCA III型映射到16q22.1的相同区域。我们报告了三个Miyakonojo和一个鹿儿岛家庭与纯粹的小脑共济失调和疾病位点在16q22.1。我们的精细连锁数据表明，16 q-ADCA III型的疾病位点在标记17 msm和CTTT 01所描绘的1.25Mb间隔内。我们还筛选了关键区域内所有基因的突变。2005年，Puratrophin定位的关键区域被报道为16 q-ADCA III型的可能原因。我们在所有与16号染色体连锁的家族中筛查了突变;所有患者在5 'UTR中都有Puratrophin突变。虽然有4例患者存在纯合子Puratrophin突变，但其临床严重程度和发病年龄难以与杂合子突变患者的结果区分。此外，我们的微阵列和真实的时间I 'CR研究显示，Puratrophin mRNA的表达在杂合子和纯合子患者的淋巴细胞中均未降低。这些结果表明，Puratrophin的突变可能只是多态性之一。为了确定16 q-ADCA III型的真实的病因，我们用CGH芯片筛选关键区域的微缺失或重复。然而，我们没有检测到微缺失或重复。

The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders. Despite phenotypic differences, SCA4 and Japanese 16q-linked ADCA type III map to the same region of 16q22.1. We reported three Miyakonojo and one Kagoshima families with pure cerebellar ataxia and a disease locus at 16q22.1. Our fine linkage data suggest that the disease locus for 16q-ADCA type III is within the 1.25Mb interval delineated by markers 17msm and CTTT01. We also screened for mutations in all genes within the critical region. In 2005, Puratrophin locates critical region has been reported as a possible cause of 16q-ADCA type III. We screened the mutation in all families linked to chromosome 16; all patients had Puratrophin mutation in the 5'UTR. Although four patients had homozygous Puratrophin mutation, their clinical severities and onset ages were difficult to distinguish from the findings of patients with heterozygous mutation. In addition, our micro array and real time I'CR studies revealed the expressions of Puratrophin mRNA were not decreased in their lymphocytes from both heterozygous and homozygous patients. These finding suggest the mutation of Puratrophin should be just one of the polymorphism. To identify real cause of 16q-ADCA type III, we screened micro deletion or duplication in critical region by CGH array. However, we did not detect micro deletion or duplication.