Shaw C E, Enayat Z E, Chioza B A, Al-Chalabi A, Radunovic A, Powell J F, Leigh P N
Department of Clinical Neurosciences, Institute of Psychiatry and King's College School of Medicine and Dentistry, London, United Kingdom.
Ann Neurol. 1998 Mar;43(3):390-4. doi: 10.1002/ana.410430319.
Eight of 38 patients (21%) with familial and 5 of 175 patients (3%) with sporadic amyotrophic lateral sclerosis (ALS) had missense mutations in the SOD-1 gene. Two novel mutations were identified. One in exon 4 substituting leucine with phenylalanine (L84F) in a familial patient and the second in exon 3 at substituting glycine with serine (G72S) in an "apparently" sporadic patient. Over 60 point mutations have now been described in all five exons of SOD-1, involving 43 of the 153 residues. Hypotheses about the toxic role of mutant SOD-1 in the pathogenesis of ALS must account for this molecular diversity.
38例家族性肌萎缩侧索硬化症（ALS）患者中有8例（21%）以及175例散发性ALS患者中有5例（3%）在SOD-1基因中存在错义突变。鉴定出两个新突变。一个在家族性患者的外显子4中，亮氨酸被苯丙氨酸替代（L84F），另一个在“明显”散发性患者的外显子3中，甘氨酸被丝氨酸替代（G72S）。目前已在SOD-1的所有五个外显子中描述了60多个点突变，涉及153个残基中的43个。关于突变型SOD-1在ALS发病机制中的毒性作用的假说必须考虑到这种分子多样性。
