第48回日本神経学会総会
＜シンポジウム11-5＞西太平洋地域の筋萎縮性側索硬化症/パーキンソン痴呆複合（ALS/PDC）と関連神経変性疾患
紀伊ALS/PDCの分子遺伝学的解析
原 賢寿1）, 桑野 良三2）, 宮下 哲典2）, 小久保 康昌3）, 佐々木 良元3）, 中原 康雄4）, 後藤 順4）, 西澤 正豊1）, 葛原 茂樹3）, 辻 省次4）
1）新潟大学脳研究所神経内科〔〒951-8585 新潟県新潟市旭町通1番町757〕
2）新潟大学脳研究所生命科学リソース研究センター遺伝子機能解析分野
3）三重大学大学院医学系研究科神経内科
4）東京大学大学院医学系研究科神経内科
Recent clinical research have revealed that more than 70% of the patients with ALS/PDC, which is highly prevalent in Hohara area in the Kii peninsula, have family history. 80% of Guamanian patients, who have identical pathological findings to those of ALS/PDC in Kii, are also known to have family history with non-Mendelian trait. These facts suggest strong genetic predisposition to ALS/PDC in both Kii and Guam. However, no genes associated with ALS/PDC have been identified by molecular genetic studies using candidate gene approach. To identify the causative or susceptibility genes for ALS/PDC, we have conducted a genomewide linkage analysis for five families with ALS/PDC in Hohara. The fact that affected individuals were ascertained in successive generations suggest an autosomal dominant (AD) inheritance, while the presence of consanguinity suggests an autosomal recessive (AR) inheritance. Although we can raise possibilities of AD model with incomplete penetrance or AR model with high gene frequency (pseudo-dominant model), the mode of inheritance of ALS/PDC families is complicated and controversial. Therefore, we are also conducting model-free (non-parametric) linkage analysis to identify the disease locus without setting mode of inheritance. More family members and detailed clinical evaluations are required to obtain the convincing evidence of linkage.
(臨床神経, 47：974−976, 2007)
key words：紀伊半島のALS/PDC, 遺伝素因, 遺伝子―環境相互作用, ゲノムワイド連鎖解析, モデルフリー（ノンパラメトリック）連鎖解析
（受付日：2007年5月16日）
