Recurrent K3E mutation in Cu/Zn superoxide dismutase gene associated with amyotrophic lateral sclerosis
Recurrent K3E mutation in Cu/Zn superoxide dismutase gene associated with amyotrophic lateral sclerosis
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与肌萎缩性脊髓侧索硬化症相关的铜/锌超氧化物歧化酶基因复发性 K3E 突变
DOI：
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发表时间：
2013
影响因子：
2.8
通讯作者：
H. Kwiecinski
中科院分区：
文献类型：
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作者：
M. Kuźma;M. Berdyński;M. Morita;Yuji Takahashi;A. Kawata;K. Kaida;Beata Kaźmierczak;A. Łusakowska;J. Goto;S. Tsuji;C. Żekanowski;H. Kwiecinski
Cu/Zn超氧化物歧化酶（SOD1）基因突变是肌萎缩性侧索硬化症（ALS）最常见的遗传原因。该研究的目的是描述波兰和日本ALS患者携带K3E SOD1突变的临床表型和单倍型背景。通过直接测序、高分辨率熔融分析或基于微阵列的高通量重测序系统鉴定K3E突变。对6种成员和2例SALS患者的SOD1侧微卫星多态性标记进行了基因分型。结果表明，K3E突变是导致典型ALS的原因。中位发病年龄为54岁。临床表型在SALS和FALS病例之间没有实质性差异，具有一些熟悉的变异。92%的患者出现肢体起病。在球综合征患者中，吞咽困难多于构音障碍。61.1%的患者（首次出现症状后19-84个月）出现呼吸功能不全。中位生存期为101个月，死亡年龄为45至77岁。K3E是波兰FALS患者中最常见的SOD1突变。它独立地起源于波兰和日本人群中不同的单倍型背景。总之，复发性K3E突变导致进展相对缓慢的肢体发病ALS，具有典型表型。
Abstract Cu/Zn superoxide dismutase (SOD1) gene mutations are the most frequently reported genetic causes of amyotrophic lateral sclerosis (ALS). The objective of the study was to describe a clinical phenotype and haplotype background of Polish and Japanese ALS patients harbouring the K3E SOD1 mutation. The K3E mutation was identified by direct sequencing, high resolution melting analysis or high-throughput microarray-based resequencing system. Microsatellite polymorphic markers flanking SOD1 were genotyped in members of six kindreds and two SALS patients. Results demonstrated that the K3E mutation was responsible for classic ALS. The median age of onset was 54 years. The clinical phenotype did not substantially differ between SALS and FALS cases of either ethnic origin, with some intrafamiliar variabilities. There was a limb onset in 92% of patients. In patients with bulbar syndrome, dysphagia predominated over dysarthria. Respiratory insufficiency was found in 61.1% of patients (19–84 months after the first symptoms onset). Median survival was 101 months with age of death ranging from 45 to 77 years. K3E was the most frequent SOD1 mutation among Polish FALS patients. It originated independently, on different haplotype background in the Polish and Japanese populations. In conclusion, recurrent K3E mutation results in a relatively slowly progressing limb onset ALS with classic phenotype.
影响因子：
4
作者：
Pratt AJ;Getzoff ED;Perry JJ
通讯作者：
Perry JJ