Warner L E, Hilz M J, Appel S H, Killian J M, Kolodry E H, Karpati G, Carpenter S, Watters G V, Wheeler C, Witt D, Bodell A, Nelis E, Van Broeckhoven C, Lupski J R
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Neuron. 1996 Sep;17(3):451-60. doi: 10.1016/s0896-6273(00)80177-4.
Hereditary demyelinating peripheral neuropathies consist of a heterogeneous group of genetic disorders that includes hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie-Tooth disease (CMT), Dejerine-Sottas syndrome (DSS), and congenital hypomyelination (CH). The clinical classification of these neuropathies into discrete categories can sometimes be difficult because there can be both clinical and pathologic variation and overlap between these disorders. We have identified five novel mutations in the myelin protein zero (MPZ) gene, encoding the major structural protein (P0) of peripheral nerve myelin, in patients with either CMT1B, DSS, or CH. This finding suggests that these disorders may not be distinct pathophysiologic entities, but rather represent a spectrum of related "myelinopathies" due to an underlying defect in myelination. Furthermore, we hypothesize the differences in clinical severity seen with mutations in MPZ are related to the type of mutation and its subsequent effect on protein function (i.e., loss of function versus dominant negative).
遗传性脱髓鞘性周围神经病由一组异质性的遗传疾病组成，包括遗传性压力易感性神经病（HNPP）、夏科-马里-图斯病（CMT）、德热里纳-索塔斯综合征（DSS）和先天性髓鞘形成低下（CH）。由于这些疾病之间存在临床和病理变异及重叠，有时很难将这些神经病进行明确的临床分类。我们在患有CMT1B、DSS或CH的患者中，鉴定出髓鞘蛋白零（MPZ）基因的五个新突变，该基因编码周围神经髓鞘的主要结构蛋白（P0）。这一发现表明，这些疾病可能并非不同的病理生理实体，而是由于髓鞘形成存在潜在缺陷而代表了一系列相关的“髓鞘病”。此外，我们推测MPZ突变所见临床严重程度的差异与突变类型及其对蛋白质功能的后续影响（即功能丧失与显性负效应）有关。
