Nishino I, Noguchi S, Murayama K, Driss A, Sugie K, Oya Y, Nagata T, Chida K, Takahashi T, Takusa Y, Ohi T, Nishimiya J, Sunohara N, Ciafaloni E, Kawai M, Aoki M, Nonaka I
Department of Neuromuscular Research, National Institute of Neuroscience, Kodaira, Tokyo, Japan.
Neurology. 2002 Dec 10;59(11):1689-93. doi: 10.1212/01.wnl.0000041631.28557.c6.
Distal myopathy with rimmed vacuoles (DMRV) is an autosomal-recessive disorder with preferential involvement of the tibialis anterior muscle that starts in young adulthood and spares quadriceps muscles. The disease locus has been mapped to chromosome 9p1-q1, the same region as the hereditary inclusion body myopathy (HIBM) locus. HIBM was originally described as rimmed vacuole myopathy sparing the quadriceps; therefore, the two diseases have been suspected to be allelic. Recently, HIBM was shown to be associated with the mutations in the gene encoding the bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE).
To determine whether DMRV and HIBM are allelic.
The GNE gene was sequenced in 34 patients with DMRV. The epimerase activity in lymphocytes from eight DMRV patients was also measured.
The authors identified 27 unrelated DMRV patients with homozygous or compound-heterozygous mutations in the GNE gene. DMRV patients had markedly decreased epimerase activity.
DMRV is allelic to HIBM. Various mutations are associated with DMRV in Japan. The loss-of-function mutations in the GNE gene appear to cause DMRV/HIBM.
伴有镶边空泡的远端肌病（DMRV）是一种常染色体隐性疾病，主要累及胫骨前肌，发病于青年期，股四头肌不受累。该疾病基因座已被定位到9号染色体p1 - q1区域，与遗传性包涵体肌病（HIBM）基因座位于同一区域。HIBM最初被描述为股四头肌不受累的镶边空泡肌病；因此，这两种疾病被怀疑是等位基因。最近，研究表明HIBM与双功能酶UDP - N - 乙酰葡糖胺2 - 表异构酶/N - 乙酰甘露糖胺激酶（GNE）编码基因的突变有关。
确定DMRV和HIBM是否为等位基因。
对34例DMRV患者的GNE基因进行测序。还检测了8例DMRV患者淋巴细胞中的表异构酶活性。
作者在27例无关的DMRV患者中发现了GNE基因的纯合或复合杂合突变。DMRV患者的表异构酶活性显著降低。
DMRV与HIBM是等位基因。在日本，多种突变与DMRV相关。GNE基因的功能丧失突变似乎导致了DMRV/HIBM。
