| Research Abstract |
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
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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
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