Ohata Takako, Yoshida Kunihiro, Sakai Haruya, Hamanoue Haruka, Mizuguchi Takeshi, Shimizu Yusaku, Okano Tomomi, Takada Fumio, Ishikawa Kinya, Mizusawa Hidehiro, Yoshiura Ko-Ichiro, Fukushima Yoshimitsu, Ikeda Shu-Ichi, Matsumoto Naomichi
Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Department of Medical Genetics, Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Sagamihara, 228-8555, Japan.
J Hum Genet. 2006;51(5):461-466. doi: 10.1007/s10038-006-0385-6. Epub 2006 Apr 14.
The molecular bases of autosomal dominant cerebellar ataxia (ADCA) have been increasingly elucidated, but 17-50% of ADCA families still remain genetically undefined in Japan. In this study we investigated 67 genetically undefined ADCA families from the Nagano prefecture, and found that 63 patients from 51 families possessed the -16C>T change in the puratrophin-1 gene, which was recently found to be pathogenic for 16q22-linked ADCA. Most patients shared a common haplotype around the puratrophin-1 gene. All patients with the -16C>T change had pure cerebellar ataxia with middle-aged or later onset. Only one patient in a large, -16C>T positive family did not have this change, but still shared a narrowed haplotype with, and was clinically indistinguishable from, the other affected family members. In Nagano, 16q22-linked ADCA appears to be much more prevalent than either SCA6 or dentatorubral-pallidoluysian atrophy (DRPLA), and may explain the high frequency of spinocerebellar ataxia.
常染色体显性遗传性小脑共济失调（ADCA）的分子基础已越来越清晰，但在日本仍有17% - 50%的ADCA家系在基因上尚未明确。在本研究中，我们调查了来自长野县的67个基因未明确的ADCA家系，发现51个家系中的63名患者在嘌呤营养蛋白-1基因中存在-16C>T突变，该突变最近被发现是与16q22连锁的ADCA的致病原因。大多数患者在嘌呤营养蛋白-1基因周围共享一个常见单倍型。所有发生-16C>T突变的患者均患有单纯性小脑共济失调，发病年龄在中年或中年以后。在一个-16C>T突变阳性的大家系中，只有一名患者没有这种突变，但仍与其他患病家庭成员共享一个缩小的单倍型，且在临床上无法区分。在长野，与16q22连锁的ADCA似乎比脊髓小脑共济失调6型（SCA6）或齿状核红核苍白球路易体萎缩症（DRPLA）更为常见，这可能解释了脊髓小脑共济失调的高发病率。
