遗传性神经病的分子基础。

Neurogenetics Laboratory, Division of Genetics and Development, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA.

Phys Med Rehabil Clin N Am. 2001 May;12(2):277-91.

Inherited disorders of peripheral nerves represent a common group of neurologic diseases. Charcot-Marie-Tooth neuropathy type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B) and to another unknown autosome (CMT1C). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-12, or in rare patients may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (P0 or MPZ) gene. The molecular defect in CMT1C is unknown. X-linked Charcot-Marie-Tooth neuropathy (CMTX), which has clinical features similar to CMT1, is associated with mutations in the connexin32 gene. Charcot-Marie-Tooth neuropathy type 2 (CMT2) is an axonal neuropathy, also of undetermined cause. Forms of CMT2 map to chromosome 1p36 (CMT2A), chromosome 3p (CMT2B), chromosome 7p (CMT2D), and to chromosome 8p21 (CMT2E). Dejerine-Sottas disease (DSD), also called hereditary motor and sensory neuropathy type III (HMSNIII), is a severe, infantile-onset, demyelinating polyneuropathy syndrome that may be associated with point mutations in either the PMP22 gene or the P0 gene and shares considerable clinical and pathologic features with CMT1. Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder that results in a recurrent, episodic demyelinating neuropathy. HNPP is associated with a 1.5-Mb deletion in chromosome 17p11.2-12 and results from reduced expression of the PMP22 gene. CMT1A and HNPP are reciprocal duplication/deletion syndromes originating from unequal crossover during germ cell meiosis. Other rare forms of demyelinating peripheral neuropathies map to chromosomes 8q, 10q, and 11q. Hereditary neuralgic amyotrophy (familial brachial plexus neuropathy) is an autosomal dominant disorder causing painful, recurrent brachial plexopathies and maps to chromosome 17q25.

遗传性周围神经病是一组常见的神经系统疾病。1型夏科-马里-图斯病（CMT1）是一组基因异质性的慢性脱髓鞘性多发性神经病，其基因位点定位于17号染色体（CMT1A）、1号染色体（CMT1B）以及另一条未知常染色体（CMT1C）。CMT1A最常与17p11.2 - 12染色体上1.5兆碱基（Mb）的串联重复相关，或者在罕见患者中可能由外周髓鞘蛋白22（PMP22）基因的点突变引起。CMT1B与髓鞘蛋白零（P0或MPZ）基因的点突变有关。CMT1C的分子缺陷尚不清楚。X连锁型夏科-马里-图斯病（CMTX），其临床特征与CMT1相似，与连接蛋白32基因的突变有关。2型夏科-马里-图斯病（CMT2）是一种轴索性神经病，病因也未明确。CMT2的不同类型基因位点定位于1p36染色体（CMT2A）、3p染色体（CMT2B）、7p染色体（CMT2D）以及8p21染色体（CMT2E）。德热里纳-索塔斯病（DSD），也称为遗传性运动和感觉神经病III型（HMSNIII），是一种严重的婴儿期起病的脱髓鞘性多发性神经病综合征，可能与PMP22基因或P0基因的点突变有关，并且与CMT1有相当多的临床和病理特征。遗传性压力易感性神经病（HNPP）是一种常染色体显性疾病，导致复发性、发作性脱髓鞘性神经病。HNPP与17p11.2 - 12染色体上1.5 Mb的缺失有关，是由PMP22基因表达减少引起的。CMT1A和HNPP是源于生殖细胞减数分裂期间不等交换的相互重复/缺失综合征。其他罕见的脱髓鞘性周围神经病类型基因位点定位于8q、10q和11q染色体。遗传性神经性肌萎缩（家族性臂丛神经病）是一种常染色体显性疾病，导致疼痛性、复发性臂丛神经病变，基因位点定位于17q25染色体。