Oculopharyngeal muscular dystrophy in Japan : studies on muscle pathology, immunohistochemistry, and molecular biology

日本眼咽型肌营养不良症：肌肉病理学、免疫组织化学和分子生物学研究

• 批准号: 08670718
• 负责人: UYAMA Eiichiro
• 金额: $ 1.47万
• 依托单位: Kumamoto 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-08670718/
• 关键词: oculopharyngeal muscular dystrophy; autosomal dominant dsiorder; two point linkage analysis; haplotype analysis; 14q11.2-q13; intranuclear tubulofilamentous inclusions; ptosis; dysphagia; 14q11・.2-q13

Oculopharyngeal muscular dystrophy (OPMD), an autosomal dominant disorder characterized by late-onset ptosis and dysphagia, and the presence of intranuclear tubulofilamentous inclusions (ITFI) of 8.5 nm outer diameter. The gene locus has recently mapped to chromosome 14q11.2-13q in French Canadian families, whose common ancestor emigrated from France to Quebec in 1634. Thus far morphologically-confirmed OPMD families have been documented in more than 15 white communities around the world. However, its occurrence in Orientals has been uncertain.In 1996, we have identified two unrelated Japanese OPMD families, including 30 affected individuals^<1), 8)>. OPMD-specific ITFI were observed in 2 to 5% of the nuclei in four different biopsied skeletal muscles^<2)>. We newly indicated that aerodynamic examination was useful to evaluate velopharyngeal closure function in OPMD patients^<2)>. To confirm the OPMD locus, we typed microsatellite markers localized to 14q in a large Shizuoka family inc … More luding 25 affected individuals^<3)>. Above 3 lod scores were obtained for all of the following five markers : 5.26 (D14S50), 3.60 (D14S283), 3.23 (D14S990), 5.04 (MYH7.24), and 4.87 (MYH7.1) at THETA=0. Thus, the gene for OPMD in Japanese cases is located on the same region of 14q as in French Canadians^<3), 6)>. Typing for another small family of Kumamoto also showed no recombination and affected individuals shared same haplotype for candidate region^<7), 9)>. However, their haplotypes were apparently different from that of Shizuoka family. We suggest that several different mutations in the OPMD gene may cause homogenous phenotype.Very recently, we identified more 4 OPMD families in Kumamoto Prefecture, locating in the center of Kyushu, Southern Japan^<6), 7)>. Furthermore, we found two adult Japanese siblings with autosomal recessive oculopharyngodistal myopathy in Kumamoto^<4), 5)>. Their phenotype is distinct from distal myopathy with rimmed vacuoles and OPMD, but shares some ultrastructual characteristics with distal myopathy with rimmed vacuoles and hereditary inclusion body myopathy. Less

眼咽肌营养不良症（OPMD）是一种常染色体显性遗传疾病，其特征为迟发性上睑下垂和吞咽困难，以及存在外径为8.5 nm的核内管状丝状包涵体（ITFI）。该基因位点最近被定位于法裔加拿大家庭的染色体14 q11.2 - 13 q，其共同祖先于1634年从法国移民到魁北克。到目前为止，形态学上确认的OPMD家族已经在世界各地超过15个白色社区中被记录。在1996年，我们鉴定了两个无关的日本OPMD家系，包括30个患病个体^<1），8）>。在四种不同的骨骼肌活检标本中，在2 - 5%的细胞核中观察到OPMD特异性ITFI ^<2）>。我们新发现空气动力学检查对评价OPMD患者的咽闭合功能是有用的^<2）>。为了确认OPMD基因座，我们在一个大的静冈家庭中定位于14 q的微卫星标记， ...更多信息 包括25名受影响的个体^<3）>。在THETA=0时，所有以下5个标记均获得了3个以上的lod评分：5.26（D14 S50）、3.60（D14 S283）、3.23（D14 S990）、5.04（MYH7.24）和4.87（MYH7.1）。因此，日本人的OPMD基因与法裔加拿大人的OPMD基因位于相同的14 q区域^<3），6）>。对另一个熊本小家族的分型也显示没有重组，并且受影响的个体在候选区域具有相同的单倍型^<7），9）>。但它们的单倍型与静冈家系的单倍型明显不同。最近，我们在日本南部九州市中心的熊本县发现了4个以上的OPMD家系^<6），7）>。此外，我们在熊本发现了两名患有常染色体隐性遗传性眼咽远端肌病的日本成年同胞^<4），5）>。它们的表型与边缘空泡型远端肌病和OPMD不同，但与边缘空泡型远端肌病和遗传性包涵体肌病具有某些超微结构特征。少

项目成果

Uyama E,et al.: "Autosomal recessive oculopharyngodistal myopathy in light of distal myopathy with rimmed vacuoles and oculopharyngeal muscular dystrophy" Neuromusc Disord. (in press).

Uyama E 等人：“常染色体隐性遗传性眼咽远端肌病，伴有边缘空泡和眼咽肌营养不良的远端肌病”神经肌肉疾病。

Uyama E, et al.: "Autosomal recessive oculopharyngodistal myopathy in light of distal myopathy with rimmed vacuoles and oculopharyngeal muscular dystrophy" Neuromusc Disord. (in press).

Uyama E 等人：“常染色体隐性遗传性眼咽远端肌病，伴有边缘空泡和眼咽肌营养不良的远端肌病”神经肌肉疾病。

Uyama E, et al.: "Oculopharyngeal muscular dystrophy in Japan." Neuromusc Disord. 7. S41-S49 (1997)

Uyama E 等人：“日本的眼咽肌营养不良症”。

Uyama E,Uchino M,Chateau D,Tome FMS.: "Autosomal recessive oculopharyngodistal myopathy in light of distal myopathy with rimmed vacuoles and oculopharyngeal muscular dystrophy." Neuromusc Disord. (in press). (1998)

Uyama E，Uchino M，Chateau D，Tome FMS.：“常染色体隐性遗传性眼咽远端肌病，伴有边缘空泡和眼咽肌营养不良的远端肌病。”

宇山英一郎(分担): "眼咽頭筋ジストロフィー「ここまでわかった筋ジストロフィー」" 医学書院(印刷中),

Eiichiro Uyama（撰稿人）：“眼咽型肌营养不良症：迄今为止我们对肌营养不良症的了解”Igakushoin（正在出版），