Inoue Ken, Shilo Konstantin, Boerkoel Cornelius F, Crowe Carol, Sawady Joram, Lupski James R, Agamanolis Dimitri P
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Ann Neurol. 2002 Dec;52(6):836-42. doi: 10.1002/ana.10404.
A unique phenotype of Waardenburg-Hirschsprung disease (WS4) accompanied by peripheral neuropathy and central dysmyelination has been recognized recently in association with SOX10 mutations. We report an infant boy with lethal congenital hypomyelinating neuropathy and WS4 who had a heterozygous SOX10 mutation (Q250X). Histopathological studies showed an absence of peripheral nerve myelin despite normal numbers of Schwann cells and profound dysmyelination in the central nervous system. These observations suggest that some SOX10 mutations such as Q250X may allow Schwann cells and oligodendrocytes to proliferate but interfere with further differentiation to form myelin. In contrast with the SOX10 loss-of-function mutations causing only WS4, mutations associated with both peripheral and central dysmyelination may affect pathology through a dominant-negative mechanism.
最近发现，伴有周围神经病变和中枢性髓鞘形成异常的瓦登伯革-赫什朋病（WS4）的一种独特表型与SOX10突变有关。我们报告了一名患有致死性先天性髓鞘形成低下性神经病变和WS4的男婴，他有一个杂合的SOX10突变（Q250X）。组织病理学研究显示，尽管施万细胞数量正常，但周围神经髓鞘缺失，且中枢神经系统存在严重的髓鞘形成异常。这些观察结果表明，某些SOX10突变（如Q250X）可能使施万细胞和少突胶质细胞增殖，但会干扰其进一步分化以形成髓鞘。与仅导致WS4的SOX10功能丧失突变不同，与周围和中枢髓鞘形成异常均相关的突变可能通过显性负性机制影响病理过程。
