Frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese patients with amyotrophic lateral sclerosis

被引:10
作者
Gromicho, Marta [1 ,2 ]
Pinto, Susana [1 ,2 ,3 ]
Gisca, Eugeniu [1 ,2 ]
Pronto-Laborinho, Ana Catarina [1 ,2 ]
Andersen, Peter M. [3 ]
de Carvalho, Mamede [1 ,2 ,4 ]
机构
[1] Univ Lisbon, Fac Med, Inst Med Mol, Ave Prof Egas Moniz, P-1648028 Lisbon, Portugal
[2] Univ Lisbon, Fac Med, Inst Physiol, Ave Prof Egas Moniz, P-1648028 Lisbon, Portugal
[3] Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden
[4] Hosp Santa Maria CHLN, Dept Neurosci & Mental Hlth, Lisbon, Portugal
关键词
Amyotrophic lateral sclerosis; C9orf72 hexanucleotide repeat expansion; SOD1; Mutation; Phenotype; Frontotemporal dementia; ALS PATIENTS; CLINICAL CHARACTERISTICS; GENETIC-HETEROGENEITY; POPULATION; DISEASE; EPIDEMIOLOGY; PATHOGENESIS; DIAGNOSIS; FEATURES; CRITERIA;
D O I
10.1016/j.neurobiolaging.2018.05.009
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
Mutation frequency of the 2 main amyotrophic lateral sclerosis (ALS) erelated genes, C9orf72 and SOD1, varies considerably across the world. We analyzed those genes in a large population of Portuguese ALS patients (n = 371) and recorded demographic and clinical features. Familial ALS (FALS) was disclosed in 11.6% of patients. Mutations in either SOD1 or C9orf72 were found in 9.2% of patients and accounted for 40% of FALS and 5.2% of sporadic ALS. SOD1 mutations were rare (0.83%), but a novel and probably disease-causing mutation was identified: p. Ala152Pro (c. 457G>C). The C9orf72 hexanucleotide repeat expansion was the commonest abnormality, accounting for 4.6% of sporadic ALS and 37.5% of FALS; in these patients, Frontotemporal Dementia was prevalent. This first report on the frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese ALS patients reiterate that the genetic architecture of ALS varies among different geographic regions. The mutations incidence in ALS patients (w10%) and associated phenotypes suggest that genetic tests should be offered to more patients, and other genes should be investigated in our population. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:325.e7 / 325.e15
页数:9
相关论文
共 61 条
[1]   ALSoD: A user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics [J].
Abel, Olubunmi ;
Powell, John F. ;
Andersen, Peter M. ;
Al-Chalabi, Ammar .
HUMAN MUTATION, 2012, 33 (09) :1345-1351
[2]   C9ORF72 hexanucleotide repeat expansion in ALS patients from the Central European Russia population [J].
Abramycheva, Natalya Y. ;
Lysogorskaia, Elena V. ;
Stepanova, Maria S. ;
Zakharova, Maria N. ;
Kovrazhkina, Elena A. ;
Razinskaya, Olga D. ;
Smirnov, Andrey P. ;
Maltsev, Andrey V. ;
Ustyugov, Alexey A. ;
Kukharsky, Michail S. ;
Khritankova, Inna V. ;
Bachurin, Sergey O. ;
Cooper-Knock, Johnathan ;
Buchman, Vladimir L. ;
Illarioshkin, Sergey N. ;
Skvortsova, Veronika I. ;
Ninkina, Natalia .
NEUROBIOLOGY OF AGING, 2015, 36 (10) :2908.e5-2908.e9
[3]   A method and server for predicting damaging missense mutations [J].
Adzhubei, Ivan A. ;
Schmidt, Steffen ;
Peshkin, Leonid ;
Ramensky, Vasily E. ;
Gerasimova, Anna ;
Bork, Peer ;
Kondrashov, Alexey S. ;
Sunyaev, Shamil R. .
NATURE METHODS, 2010, 7 (04) :248-249
[4]   Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study [J].
AI-Chalabi, Ammar ;
Calvo, Andrea ;
Chio, Adriano ;
Colville, Shuna ;
Ellis, Cathy M. ;
Hardiman, Oda ;
Heverin, Mark ;
Howard, Robin S. ;
Huisman, Mark H. B. ;
Keren, Noa ;
Leigh, P. Nigel ;
Mazzini, Letizia ;
Mora, Gabriele ;
Orrell, Richard W. ;
Rooney, James ;
Scott, Kirsten M. ;
Scotton, William J. ;
Seelen, Meinie ;
Shaw, Christopher E. ;
Sidle, Katie S. ;
Swingler, Robert ;
Tsuda, Miho ;
Veldink, Jan H. ;
Visser, Anne E. ;
van den Berg, Leonard H. ;
Pearce, Neil .
LANCET NEUROLOGY, 2014, 13 (11) :1108-1113
[5]   A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories [J].
Akimoto, Chizuru ;
Volk, Alexander E. ;
van Blitterswijk, Marka ;
Van den Broeck, Marleen ;
Leblond, Claire S. ;
Lumbroso, Serge ;
Camu, William ;
Neitzel, Birgit ;
Onodera, Osamu ;
van Rheenen, Wouter ;
Pinto, Susana ;
Weber, Markus ;
Smith, Bradley ;
Proven, Melanie ;
Talbot, Kevin ;
Keagle, Pamela ;
Chesi, Alessandra ;
Ratti, Antonia ;
van der Zee, Julie ;
Alstermark, Helena ;
Birve, Anna ;
Calini, Daniela ;
Nordin, Angelica ;
Tradowsky, Daniela C. ;
Just, Walter ;
Daoud, Hussein ;
Angerbauer, Sabrina ;
DeJesus-Hernandez, Mariely ;
Konno, Takuya ;
Lloyd-Jani, Anjali ;
de Carvalho, Mamede ;
Mouzat, Kevin ;
Landers, John E. ;
Veldink, Jan H. ;
Silani, Vincenzo ;
Gitler, Aaron D. ;
Shaw, Christopher E. ;
Rouleau, Guy A. ;
van den Berg, Leonard H. ;
Van Broeckhoven, Christine ;
Rademakers, Rosa ;
Andersen, Peter M. ;
Kubisch, Christian .
JOURNAL OF MEDICAL GENETICS, 2014, 51 (06) :419-424
[6]   Gene discovery in amyotrophic lateral sclerosis: implications for clinical management [J].
Al-Chalabi, Ammar ;
van den Berg, Leonard H. ;
Veldink, Jan .
NATURE REVIEWS NEUROLOGY, 2017, 13 (02) :96-104
[7]   Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene [J].
Andersen, Peter M. .
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS, 2006, 6 (01) :37-46
[8]  
[Anonymous], 2017, LANCET, DOI DOI 10.1016/S0140-6736(17)31287-4
[9]   Familial Amyotrophic Lateral Sclerosis [J].
Boylan, Kevin .
NEUROLOGIC CLINICS, 2015, 33 (04) :807-+
[10]   The frontotemporal dementia-motor neuron disease continuum [J].
Burrell, James R. ;
Halliday, Glenda M. ;
Kril, Jillian J. ;
Ittner, Lars M. ;
Gotz, Jurgen ;
Kiernan, Matthew C. ;
Hodges, John R. .
LANCET, 2016, 388 (10047) :919-931