De Jonghe P, Timmerman V, Ceuterick C, Nelis E, De Vriendt E, Löfgren A, Vercruyssen A, Verellen C, Van Maldergem L, Martin J J, Van Broeckhoven C
Department of Biochemistry, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UIA), University Hospital Antwerpen (UZA), Belgium.
Brain. 1999 Feb;122 ( Pt 2):281-90. doi: 10.1093/brain/122.2.281.
We observed a missense mutation in the peripheral myelin protein zero gene (MPZ, Thr124Met) in seven Charcot-Marie-Tooth (CMT) families and in two isolated CMT patients of Belgian ancestry. Allele-sharing analysis of markers flanking the MPZ gene indicated that all patients with the Thr124Met mutation have one common ancestor. The mutation is associated with a clinically distinct phenotype characterized by late onset, marked sensory abnormalities and, in some families, deafness and pupillary abnormalities. Nerve conduction velocities of the motor median nerve vary from <38 m/s to normal values in these patients. Clusters of remyelinating axons in a sural nerve biopsy demonstrate an axonal involvement, with axonal regeneration. Phenotype-genotype correlations in 30 patients with the Thr124Met MPZ mutation indicate that, based on nerve conduction velocity criteria, these patients are difficult to classify as CMT1 or CMT2. We therefore conclude that CMT patients with slightly reduced or nearly normal nerve conduction velocity should be screened for MPZ mutations, particularly when additional clinical features such as marked sensory disturbances, pupillary abnormalities or deafness are also present.
我们在7个夏科-马里-图斯病（CMT）家族以及2名有比利时血统的散发性CMT患者中，观察到外周髓磷脂蛋白零基因（MPZ，Thr124Met）存在错义突变。对MPZ基因侧翼标记进行的等位基因共享分析表明，所有携带Thr124Met突变的患者都有一个共同祖先。该突变与一种临床特征明显不同的表型相关，其特点为发病较晚、有明显的感觉异常，在一些家族中还伴有耳聋和瞳孔异常。这些患者运动正中神经的神经传导速度在<38 m/s至正常数值之间变化。腓肠神经活检中再髓鞘化轴突簇显示存在轴突受累，并伴有轴突再生。对30名携带Thr124Met MPZ突变患者的表型-基因型相关性分析表明，根据神经传导速度标准，这些患者很难归类为CMT1或CMT2。因此我们得出结论，对于神经传导速度略有降低或接近正常的CMT患者，应筛查MPZ突变，尤其是当还存在明显感觉障碍、瞳孔异常或耳聋等其他临床特征时。
