A novel p.Ser108LeufsTer15 SOD1 mutation leading to the formation of a premature stop codon in an apparently sporadic ALS patient: insights into the underlying pathomechanisms

被引：5

作者：

Canosa, Antonio ^{[1
]}

De Marco, Giovanni ^{[1
]}

Lomartire, Annarosa ^{[1
]}

Rinaudo, Maria Teresa ^{[2
]}

Di Cunto, Ferdinando ^{[3
]}

Turco, Emilia ^{[4
]}

Barberis, Marco ^{[1
]}

Brunetti, Maura ^{[1
]}

Casale, Federico ^{[1
]}

Moglia, Cristina ^{[1
,5
]}

Calvo, Andrea ^{[1
,5
,6
]}

Marklund, Stefan L. ^{[7
]}

Andersen, Peter M. ^{[8
]}

Mora, Gabriele ^{[9
]}

Chio, Adriano ^{[1
,5
,6
,10
]}

机构：

[1] Univ Turin, Rita Levi Montalcini Dept Neurosci, ALS Ctr, Via Cherasco 15, I-10126 Turin, Italy

[2] Univ Turin, Dept Oncol, Turin, Italy

[3] Univ Turin, Neurosci Inst Cavalieri Ottolenghi, Orbassano, Italy

[4] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy

[5] Univ Citta Salute & Sci Torino, Azienda Osped, SC Neurol 2 U, Turin, Italy

[6] NIT, Turin, Italy

[7] Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden

[8] Umea Univ, Clin Chem, Dept Med Biosci, Umea, Sweden

[9] IRCCS, ALS Ctr, Salvatore Maugeri Clin Sci Inst, Neurol Rehabil Unit, Milan, Italy

[10] CNR, Inst Cognit Sci & Technol, Rome, Italy

来源：

NEUROBIOLOGY OF AGING | 2018年 / 72卷

关键词：

Amyotrophic lateral sclerosis; SOD1; Truncated protein; Frameshift mutation; Oxidative stress; Protein aggregation; AMYOTROPHIC-LATERAL-SCLEROSIS; CU/ZN SUPEROXIDE-DISMUTASE; BASE-PAIR DELETION; MUTANT SOD1; INSERTION MUTATION; GENE; IDENTIFICATION; FRAMESHIFT; DISEASE; REDUCE;

D O I：

10.1016/j.neurobiolaging.2018.08.014

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

We report an apparently sporadic amyotrophic lateral sclerosis patient carrying a heterozygous novel frameshift SOD1 mutation (p.Ser108LeufsTer15), predicted to cause a premature protein truncation. RTPCR analysis of SOD1 mRNA and SDS-PAGE/Western blot analysis of PBMC demonstrated that mRNA from the mutant allele is expressed at levels similar to those of the wild-type allele, but the truncated protein is undetectable also in the insoluble fraction and after proteasome inhibition. Accordingly, the dismutation activity in erythrocytes is halved. Thus, the pathogenic mechanism associated with this mutation might be based on an insufficient activity of SOD1 that would make motor neurons more vulnerable to oxidative injury. However, it cannot be excluded that p.Ser108LeufsTer15 SOD1 is present in the nervous tissue and, being less charged and hence having less repulsive forces than the wild-type protein, may trigger toxic mechanisms as a consequence of its propensity to aggregate. (C) 2018 Elsevier Inc. All rights reserved.

引用

页码：189.e11 / 189.e17

页数：7

共 27 条

[1] True sporadic ALS associated with a novel SOD-1 mutation [J].