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

眼咽肌营养不良症(OPMD)是一种常染色体显性遗传性疾病，以晚发的上睑下垂和吞咽困难为特征，并存在外径8.5 nm的核内管丝状包涵体(ITFI)。该基因座最近被定位在14q11.2-13q的法裔加拿大家庭中，他们的共同祖先于1634年从法国移民到魁北克。到目前为止，世界各地超过15个白人社区记录了经形态证实的OPMD家庭。然而，它在东方人中的出现一直是不确定的。1996年，我们发现了两个不相关的日本OPMD家系，包括30个受影响的个体。OPMD特异性的ITFI在四种不同的骨骼肌中观察到2%到5%的细胞核。我们新发现空气动力学检查有助于评价OPMD患者的腭咽闭合功能。为了确认OPMD基因座，我们在静冈公司的一个大家族…中输入了定位于14Q的微卫星标记更多25名受影响的个人。在Theta=0时，以下5个标记均获得3分以上的Lod评分：5.26(D14S50)、3.60(D14S283)、3.23(D14S990)、5.04(MYH7.24)和4.87(MYH7.1)。因此，日本人的OPMD基因位于与法裔加拿大人相同的14q区域。另一个熊本小家系的基因分型也没有重组，受影响的个体在候选区域^&lt；7)，9)&gt；共享相同的单倍型。然而，它们的单倍型与静冈家族的单倍型明显不同。我们认为OPMD基因的几个不同突变可能导致同源表型。最近，我们在熊本县发现了4个OPMD家系，位于日本南部九州的中心。此外，我们还发现了两个患有常染色体隐性遗传性眼咽远端肌病的成年日本兄弟姐妹，位于熊本氏4)、5)和gt；它们的表型不同于远端空泡肌病和OPMD，但与远端空泡肌病和遗传性包涵体肌病有一定的超微结构特征。较少

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