Xu Min, Da Yu-wei, Liu Lu, Wang Fen, Jia Jian-ping
1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
J Child Neurol. 2013 Oct;28(10):1316-9. doi: 10.1177/0883073812467688. Epub 2012 Dec 17.
Giant axonal neuropathy is a rare autosomal recessive disorder, which typically involves both central and peripheral nervous system. Yet the phenotypic-genotypic correlation remains obscure. We report a novel compound heterozygous mutation with the c. 805C>T in exon 4(Arg545His missense mutation) and the c. 1634G>A in exon 11(Arg269Trp missense mutation) in an 11-year-old Chinese giant axonal neuropathy case. This patient had an atypical giant axonal neuropathy phenotype rather similar to Charcot-Marie-Tooth disease, without tightly curled hair and mental retardation. The patient had a slowly progressive sensory motor neuropathy since age 3 years, and she also had nystagmus, feet deformities, scoliosis, and cerebellar tonsillar protrusion. Electrophysiological studies indicated a predominantly axonal sensory-motor neuropathy. The diagnosis was confirmed by sural nerve biopsy and direct sequencing of all the 11 gigaxonin exons. The proband's parents are heterozygotes of the disease without symptoms. Our findings extend the number of gigaxonin mutations that cause giant axonal neuropathy.
巨大轴索神经病是一种罕见的常染色体隐性疾病，通常累及中枢和周围神经系统。然而，其表型-基因型的相关性仍不明确。我们报告了一例11岁中国巨大轴索神经病患者，其外显子4存在新的复合杂合突变c.805C>T（R545H错义突变），外显子11存在c.1634G>A（R269W错义突变）。该患者具有非典型的巨大轴索神经病表型，与夏科-马里-图斯病颇为相似，无紧密卷曲毛发和智力发育迟缓。患者自3岁起出现缓慢进展的感觉运动神经病，还伴有眼球震颤、足部畸形、脊柱侧弯和小脑扁桃体下疝。电生理研究表明主要为轴索性感觉运动神经病。经腓肠神经活检及对所有11个伴肌动蛋白编码基因外显子进行直接测序，确诊了该病。先证者的父母是该疾病的杂合子，无症状。我们的发现增加了导致巨大轴索神经病的伴肌动蛋白编码基因突变的数量。
