Hereditary motor neuron disease in a large Norwegian family with a 鈥淗46R鈥?substitution in the superoxide dismutase 1 gene

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• 作者：Rune Ø ; stern^a ; ^b ; ¹ ; ^{Rune.Andre.Helland.Ostern@unn.no} ; Toril Fagerheim^b ; ¹ ; Kristin Ø ; rstavik^c ; Trygve Holmø ; y^e ; Arvid Heiberg^d ; Inger Lund-Petersen^c ; Tim M. Strom^f ; Ø ; ivind Nilssen^a ; ^b ; Arve Dahl^c ; ²
• 关键词：H46R ; SOD1 ; HMN ; ALS ; p.His47Arg
• 刊名：Neuromuscular Disorders
• 出版年：2012
• 期刊代码：203_09608966
• 类别：med
• 出版时间：June, 2012
• 卷：22
• 期：6
• 页码：511-521
• 文件大小：360 K

摘要

Mutant genes associated with Charcot Marie Tooth type 2, distal hereditary motor neuropathy and familial amyotrophic lateral sclerosis may cause overlapping clinical phenotypes. We performed whole genome linkage analysis, haplotype analysis, sequencing and detailed clinical and neurophysiological investigations in a large Norwegian kindred with a condition that clinically had been classified as Charcot Marie Tooth type 2. The mutation c.140A>G, p.His47Arg (alias p.His46Arg or H46R) in the superoxide dismutase 1 gene (SOD1) segregated with the disease. The patients present a hereditary motor neuropathy-like clinical picture and long survival (mean 29 years). To our knowledge, this is the first extensive report describing a large non-Japanese kindred. The prognostic implications of the condition seen in this family have little in common with what is normally associated with sporadic amyotrophic lateral sclerosis and illustrates the complexity of the genetic etiology of lower motor neuron disease.