Linkage analysis of paroxysmal kinesigenic choreoatherosis

阵发性运动源性舞蹈动脉粥样硬化的连锁分析

• 批准号: 08670930
• 负责人: MATSUISHI Toyojiro
• 金额: $ 1.02万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670930/
• 关键词: paroxysmal kinesigenic choreoathetosis; autosomal dominant; linkage analysis; 16p; 常染色体優勢遺伝; SSCP; 不随意運動発作症(PKC); Paroxysmal dystonic choreoathetosis(PDC); イオンチャンネル

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.

为了对阵发性动态性舞蹈病（PKC）进行连锁分析，我们在日本进行了多中心调查。向包括229家医疗机构在内的日本儿童神经病学学会理事会的所有成员邮寄了一份调查表。回复率为78%。我们分析了101例PKC患者，包括53例散发患者和48例来自32个家庭的患者。101例中男性81例，32个家族中56%为常染色体显性遗传，具有完全外显性，22%为不完全外显性。最近，家族性婴儿惊厥和阵发性舞蹈病（ICCA）的基因位点与人类16号染色体的中心点周围区域有关[Szepetowski等，1997]。我们研究了四个日本家庭，其中PKC作为常染色体显性性状遗传，并伴有可变表达的婴儿惊厥。人类基因组用微卫星标记进行定时间隔筛选。标记选择在D16S420、D16S411、D16S3133、D16S3093附近。D16S3093的最大2点LOD评分为2.408148，其他标记包括D16S3133 （LOD评分2.107205）、D16S420 （LOD评分1.786341）、D16S411 （LOD评分1.786342）。日本PKC家族性病例强烈提示与16号染色体的着丝粒周围区域有关。β -2型酪氨酸激酶C位于D16S420和D16S411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，钠通道的三γ亚基，钠/葡萄糖共转运蛋白和atp酶，钙转运蛋白由位于感兴趣区域的基因编码。我们正在计划候选基因的SSCP分析。

项目成果

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周广西：“帕金森病脑脊液中 β-苯乙胺的减少。”J Neurol Neurosurg Psychiatry 63.6 (1997)。

Toyojiro Matsuishi, Shinichiro Nagamitsu, Yushiro Yamashita, Yoshihiko Murakami, Akihiko Kimura, Tetsuo Sakai, Hiroshi Shoji, Hirohisa Kato, Alan K Percy: "Decreased cerebrospinal fluid levels of substance P in patients with Rett syndrome" Ann Neuro. 42.

Toyojiro Matsuishi、Shinichiro Nagamitsu、Yushiro Yamashita、Yoshihiko Murakami、Akihiko Kimura、Tetsuo Sakai、Hiroshi Shoji、Hirohisa Kato、Alan K Percy：“Rett 综合征患者脑脊液 P 物质水平降低”Ann Neuro。

Shinichiro Nagamitsu: "CSF β-endorphin levels in patients with infantile autism." J Autism Dev Disord. 27.2. 155-163 (1997)

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Toyojiro Matsuishi: "Decreased Cerebrospinal fluid levels of substance P in patients with Rett syndrome." Ann Neurol. 42.6. 978-981 (1997)

Toyojiro Matsuishi：“Rett 综合征患者脑脊液 P 物质水平降低。”