Linkage analysis of paroxysmal kinesigenic choreoatherosis

为了进行阵发性运动诱发性舞蹈手足徐动症（PKC）的连锁分析，我们在日本进行了多中心调查。问卷邮寄给日本儿童神经学会理事会的所有成员，包括229个医疗机构。答复率为78%。我们分析了101例PKC患者，其中包括53例散发患者和32个家族中的48例患者。101例患者中男性81例，32个家系中56%为完全显性遗传，22%为不完全显性遗传。最近，家族性婴儿惊厥和阵发性舞蹈手足徐动症（ICCA）的基因位点与人类16号染色体的着丝粒周围区域连锁[Szepetowski et al，1997]。我们研究了4个日本家族，其中PKC作为常染色体显性遗传性状与显性表达的婴儿惊厥一起遗传。人类基因组中筛选微卫星标记定期间隔。在D16 S420、D16 S411、D16 S3133、D16 S3093周围选择标记，D16 S3093和D16 S3133等标记获得的最大两点LOD得分为2.408148 D16 S420（LOD得分1.786341）、D16 S411（LOD得分1.786342）。日本人PKC家族性病例强烈建议连接在16号染色体的着丝粒周围区域。β 2型酪氨酸激酶C位于D16 S420和D16 S411附近。离子通道和转运蛋白也可能在PKC的发病机制中发挥作用，钠/葡萄糖协同转运蛋白钠通道的三个γ亚单位和钙转运蛋白ATP酶由位于感兴趣区域的基因编码。我们计划对候选基因进行SSCP分析。

To charity the linkage analysis of paroxysmal kinesigenic choreoathetosis (PKC), we conducted the multicenter survey in Japan. A questionnaire was mailed to all members of Council of the Child Neurology Society in Japan including 229 medical institutions. The reply rate was 78%. We analyzed 101 patients with PKC,including 53 sporadic patients and 48 patients in 32 families. Eighty one of the 101 cases were men and 56% of the 32 families revealed an autosomal dominant inheritance with complete penetrance, and 22% had incomplete penetrance. Recently, the gene locus for familial infantile convulsion and paroxysmal choreoathetosis (ICCA) linked to the pericentromeric region of human chromosome 16 [Szepetowski et al, 1997].We have studied four Japanese families in which PKC was inherited as an autosomal dominant trait together with variably expressed infantile convulsions. The human genome was screened with microsatellite markers regulary spaced. Markers were selected around D16S420, D16S411, D16S3133, D16S3093.A maximum two-point LOD score of 2.408148 was obtained with D16S3093, and other markers including D16S3133 (LOD score 2.107205), D16S420 (LOD score 1.786341), D16S411 (LOD score 1.786342) were obtained. Familial cases of Japanese PKC was strongly suggested to link in the pericentromeric region of chromosome 16.The beta-2type of tyrosin kinase C is situated around D16S420 and D16S411. Ionic channels and transporters could also play a role in the pathogenesis of PKC,tre gamma-subiunit of a sodium channel, a sodium/grucose co-transporter, and ATPase, calcium-transporting protein are encoded by genes situated in the regions of interest. We are planning the SSCP analysis of candidate genes.