Patel P I, Roa B B, Welcher A A, Schoener-Scott R, Trask B J, Pentao L, Snipes G J, Garcia C A, Francke U, Shooter E M, Lupski J R, Suter U
Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030.
Nat Genet. 1992 Jun;1(3):159-65. doi: 10.1038/ng0692-159.
Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a large DNA duplication on the short arm of human chromosome 17. The trembler (Tr) mouse serves as a model for CMT1A because of phenotypic similarities and because the Tr locus maps to mouse chromosome 11 in a region of conserved synteny with human chromosome 17. Recently, the peripheral myelin gene Pmp-22 was found to carry a point mutation in Tr mice. We have isolated cDNA and genomic clones for human PMP-22. The gene maps to human chromosome 17p11.2-17p12, is expressed at high levels in peripheral nervous tissue and is duplicated, but not disrupted, in CMT1A patients. Thus, we suggest that a gene dosage effect involving PMP-22 is at least partially responsible for the demyelinating neuropathy seen in CMT1A.
1A型夏科-马里-图斯病（CMT1A）是一种常染色体显性周围神经病，与人类17号染色体短臂上的大片段DNA重复有关。震颤鼠（Tr）可作为CMT1A的模型，因为其具有表型相似性，且Tr基因座定位于小鼠11号染色体上与人类17号染色体保守同线性的区域。最近，在外周髓磷脂基因Pmp - 22中发现Tr小鼠携带一个点突变。我们已分离出人类PMP - 22的cDNA和基因组克隆。该基因定位于人类17p11.2 - 17p12，在外周神经组织中高水平表达，且在CMT1A患者中发生重复但未被破坏。因此，我们认为涉及PMP - 22的基因剂量效应至少部分导致了CMT1A中所见的脱髓鞘性神经病。
