Mutations in GDAP1 -: Autosomal recessive CMT with demyelination and axonopathy
Mutations in GDAP1 -: Autosomal recessive CMT with demyelination and axonopathy
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DOI：
10.1212/01.wnl.0000036272.36047.54
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发表时间：
2002-12-24
期刊：
影响因子：
9.9
通讯作者：
Timmerman, V
中科院分区：
文献类型：
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作者：
Nelis, E;Erdem, S;Timmerman, V
背景：神经节苷脂诱导分化相关蛋白1基因(GDAP1)突变导致常染色体隐性遗传性(AR)脱髓鞘夏科-玛丽-牙病(CMT)4A型(CMT4A)以及AR轴索性CMT伴声带瘫痪。方法：对7个8q21.1染色体CMT4A基因座纯合子的AR CMT家系进行GDAP1基因编码区突变筛查。结果：发现外显子5(c.581C>；G，S194X)存在无义突变，外显子6(c.786delG，G262fsX284)存在1个碱基缺失，外显子6(c.844C>；T，R282C)存在错义突变。结论：GDAP1基因突变是AR CMT的常见原因。它们会导致早发性、严重的临床表型。神经传导速度(NCV)的范围是可变的。一些患者的NCV正常或接近正常，提示轴索神经病变，而另一些患者的NCV严重减慢，与脱髓鞘相容。周围神经活检的结果同样多变，表现为脱髓鞘和轴突变性的特征。
Background: Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) were recently shown to be responsible for autosomal recessive (AR) demyelinating Charcot-Marie-Tooth disease (CMT) type 4A (CMT4A) as well as AR axonal CMT with vocal cord paralysis. Methods: The coding region of GDAP1 was screened for the presence of mutations in seven families with AR CMT in which the patients were homozygous for markers of the CMT4A locus at chromosome 8q21.1. Results: A nonsense mutation was detected in exon 5 (c.581C>G, S194X), a 1-bp deletion in exon 6 (c.786delG, G262fsX284), and a missense mutation in exon 6 (c.844C>T, R282C). Conclusions: Mutations in GDAP1 are a frequent cause of AR CMT. They result in an early-onset, severe clinical phenotype. The range of nerve conduction velocities (NCV) is variable. Some patients have normal or near normal NCV, suggesting an axonal neuropathy, whereas others have severely slowed NCV compatible with demyelination. The peripheral nerve biopsy findings are equally variable and show features of demyelination and axonal degeneration.