Johnson-Kerner Bethany L, Roth Lisa, Greene J Palmer, Wichterle Hynek, Sproule Douglas M
Project A.L.S./Jenifer Estess Laboratory for Stem Cell Research, Center for Motor Neuron Biology and Disease, Columbia Stem Cell Initiative, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Muscle Nerve. 2014 Oct;50(4):467-76. doi: 10.1002/mus.24321.
Giant axonal neuropathy (GAN) is a rare pediatric neurodegenerative disease. It is best known for the "giant" axons caused by accumulations of intermediate filaments. The disease is progressive, with onset around age 3 years and death by the third decade of life. GAN results from recessive mutations in the GAN gene encoding gigaxonin, and our analysis of all reported mutations shows that they are distributed throughout the protein structure. Precisely how these mutations cause the disease remains to be determined. In addition to changes in peripheral nerves that are similar to those seen in neuropathies such as Charcot-Marie-Tooth type 2, GAN patients exhibit a wide range of central nervous system signs. These features, corroborated by degeneration of central tracts apparent from postmortem pathology, indicate that GAN is also a progressive neurodegenerative disease. To reflect this phenotype more precisely, we therefore propose that the disease should be more appropriately referred to as "giant axonal neurodegeneration."
巨大轴索性神经病（GAN）是一种罕见的儿科神经退行性疾病。它最出名的是由中间丝聚集导致的“巨大”轴突。这种疾病是进行性的，发病年龄约为3岁，在生命的第三个十年死亡。GAN是由编码巨大轴突素的GAN基因突变引起的隐性突变导致的，我们对所有已报道突变的分析表明，它们分布在整个蛋白质结构中。这些突变究竟如何导致该疾病仍有待确定。除了周围神经的变化与诸如2型夏科-马里-图斯病等神经病中所见的变化相似外，GAN患者还表现出广泛的中枢神经系统体征。死后病理学显示中枢神经束退化证实了这些特征，表明GAN也是一种进行性神经退行性疾病。因此，为了更准确地反映这种表型，我们建议该疾病应更恰当地称为“巨大轴突神经变性”。
