Nicholson G A
University of Sydney, Molecular Genetics Laboratory, Concord Hospital, NSW, Australia.
Ann N Y Acad Sci. 1999 Sep 14;883:383-8.
In order to determine the optimal approach for mutation testing in the form of Charcot-Marie-Tooth (CMT) neuropathy, consecutive patients with a CMT phenotype, available family history information on at least first-degree relatives, and median motor conduction velocities of less than 50 m/sec were tested for the CMT1A duplication and for connexin32, peripheral myelin protein 22 (PMP22) and myelin protein zero (P0) point mutations. A cutoff value for median motor conduction velocity of less than 50 m/sec was adopted to include all CMTX families. All of the connexin32 mutations, except for one sporadic case, were found by first selecting families with no male-to-male inheritance of CMT and neurophysiological indicators of CMTX. All PMP22 and P0 mutations were found by selecting Dejerine-Sottas cases or dominantly inherited CMT1 with a very severe phenotype. It is concluded that "blind" testing of CMT1 families for connexin32, P0, and PMP22 mutations is of limited value.
为了确定进行夏科-马里-图思（CMT）神经病形式的突变检测的最佳方法，对具有CMT表型、至少有一级亲属的可用家族史信息且运动神经传导速度中位数小于50米/秒的连续患者进行了CMT1A重复以及连接蛋白32、外周髓鞘蛋白22（PMP22）和髓鞘蛋白零（P0）点突变的检测。采用运动神经传导速度中位数小于50米/秒的临界值以纳入所有CMTX家系。除1例散发病例外，所有连接蛋白32突变均通过首先选择无CMT男性对男性遗传且具有CMTX神经生理学指标的家系而发现。所有PMP22和P0突变均通过选择德热里纳-索塔斯病例或具有非常严重表型的显性遗传CMT1而发现。得出结论，对CMT1家系进行连接蛋白32、P0和PMP22突变的“盲目”检测价值有限。
