FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS (ALS) IN JAPAN ASSOCIATED WITH H46R MUTATION IN CU/ZN SUPEROXIDE-DISMUTASE GENE - A POSSIBLE NEW SUBTYPE OF FAMILIAL ALS
FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS (ALS) IN JAPAN ASSOCIATED WITH H46R MUTATION IN CU/ZN SUPEROXIDE-DISMUTASE GENE - A POSSIBLE NEW SUBTYPE OF FAMILIAL ALS
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DOI：
10.1016/0022-510x(94)90097-3
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发表时间：
1994-10-01
影响因子：
4.4
通讯作者：
ABE, K
中科院分区：
文献类型：
--
作者：
AOKI, M;OGASAWARA, M;ABE, K
肌萎缩侧索硬化症（ALS）是一种进行性和致命的神经系统疾病，导致无情的损害运动神经元系统。虽然约5-10%的病例是家族性的，但ALS的病理生理过程仍然未知。我们发现了一个新的点突变A到G的Cu/Zn SOD基因的外显子2，导致氨基酸取代组氨酸（46）精氨酸（H46 R），在两个日本家族性ALS（FALS）的家庭。突变的分离是明显的。Cu/Zn SOD的酶活性在患病的家庭成员，与其他非患病的家庭成员相比，降低到约80%。这些家族中的患者的临床特征是相对较晚发病，最初累及下肢，相对罕见的延髓肌肉损伤和肌无力和萎缩的进展缓慢，与其他日本的FALS病例相比，没有突变的Cu/Zn SOD基因。这些发现表明Cu/Zn SOD基因中的H46 R突变与这种独特的Fals亚型高度相关。
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurological disorder that results in relentless damage to the motor neuron system. Although about 5-10% of cases are familial, the pathophysiologic process of ALS remains unknown. We identified a novel point mutation A to G in exon 2 of the Cu/Zn SOD gene, resulting in an amino acid substitution of histidine(46) by arginine (H46R), in two Japanese familial ALS (FALS) families. The segregations of the mutation were evident. The enzymatic activities of Cu/Zn SOD of peripheral red blood cell lysate were reduced to about 80% in the affected members, compared with other non-affected family members. The patients in these families are clinically characterized by relative late onset, initial involvement in lower extremities, relative rare impairment of bulbar muscles and much slow progression of muscular weakness and atrophy, compared with other Japanese FALS cases who have no mutation in the Cu/Zn SOD gene. These findings suggest that the H46R mutation in Cu/Zn SOD gene is highly related to this unique subtype of FALS.