Genetic Study of Paroxysmal Kinesigenic Choreoathetosis

阵发性运动源性舞蹈手足徐动症的遗传学研究

• 批准号: 10670770
• 负责人: MATSUISHI Toyojiro
• 金额: $ 2.11万
• 依托单位: Department of Pediatrics, 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670770/
• 关键词: Paroxysmal kinesigenic choreoathetosis; dystonia; chorea; linkage analysis; infantile convulsion; ion channel; 乳児けいれん; 日本人家系; 16p; 16

Paroxysmal kinesigenic choreoathetosis (PKC), is characterized by recurrent, brief attacks of involuntary movements induced by sudden voluntary movements or startle response. Some patients with PKC have a history of infantile afebrile convulsions with a favorable outcome. To confirm the PKC locus, we performed genomewide linkage analysis on eight Japanese families with autosomal dominant PKC.Two-point linkage analysis provided a maximum LOD score of 10.27 (recombination Fraction [θ]=.00 ; penetrance [p]=.7) at marker D16S3081, and a maximum multipoint LOD score for a subset of markers was calculated to be 11.51 (p=0.8) at D16S3080. Haplotype analysis defined the disease locus within a region of〜12.4 cM between D16S3093 and D16S416. P1-derived artificial chromosome clones containing loci D16S3093 and D16S416 were mapped, by use of FISH, to 16p11.2 and 16p12.1, respectively. Thus, in the eight families studied, the chromosomal localization of the PKC critical region (PKCR) is 16p11.2-q12.1. The PKCR overlaps with a region responsible for "infantile convulsions and paroxysmal choreoathetosis" (ICCA) (MIM 602066). Then, we performed the candidate gene analysis, those are known to locate in the PKCR.Some candidate genes that have been mapped either between D16S3093 and D16S416 include the interleukin-4-receptor α-chain gene (IL4R [MIM 147781]), the adenylate cyclase-7 gene (ADCY7 [MIM 6003585]), the protein phosphatase-4 catalytic subunit gene (PPP4C [MIM 602035]), and the monoamine-preferring sulfotransferase gene (STM [MIM 600641]), did not link to the PKC.We are doing the collaborative study of newly discovered molecule, which has been mapped in PKCR.

阵发性运动诱发性舞蹈手足徐动症（PKC）是一种由突然的随意运动或惊吓反应引起的反复、短暂的不随意运动。一些PKC患者有婴儿无热性惊厥病史，预后良好。为了确认PKC基因座，我们对八个患有常染色体显性PKC的日本家庭进行了全基因组连锁分析。两点连锁分析提供了最大LOD评分为10.27（重组分数[θ]=.00 ;在标记物D16 S3081处，最大多点LOD评分计算为11.51（p=0.8），在标记物D16 S3080处，最大多点LOD评分计算为11.51（p=0.8）。单倍型分析将疾病位点定义在D16 S3093和D16 S416之间的约12.4cM的区域内。利用FISH技术将含有D16 S3093和D16 S416位点的P1人工染色体克隆分别定位于16p11.2和16p12.1。因此，在所研究的8个家族中，PKC关键区（PKCR）的染色体定位是16p11.2-q12.1。PKCR与负责“婴儿惊厥和阵发性舞蹈手足徐动症”（ICCA）（MIM 602066）的区域重叠。在此基础上，我们对PKCR中已知的候选基因进行了分析，发现在D16 S3093和D16 S416之间定位的候选基因包括白细胞介素4受体α链基因（IL 4 R [MIM 147781]），腺苷酸环化酶-7基因（ADCY 7 [MIM 6003585]），蛋白磷酸酶-4催化亚基基因（PPP 4C [MIM 602035]）和单胺偏好磺基转移酶基因（STM [MIM 600641]），与PKC没有关联。我们正在进行新发现的分子的合作研究，该分子已被定位在PKCR中。

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