Two Italian kindreds with familial amyotrophic lateral sclerosis due to FUS mutation

被引：127

作者：

Chio, Adriano ^{[1
]}

Restagno, Gabriella ^{[2
]}

Brunetti, Maura ^{[2
]}

Ossola, Irene ^{[2
]}

Calvo, Andrea ^{[1
]}

Mora, Gabriele ^{[3
]}

Sabatelli, Mario ^{[4
,5
]}

Monsurro, Maria Rosaria ^{[6
]}

Battistini, Stefania ^{[7
]}

Mandrioli, Jessica ^{[8
]}

Salvi, Fabrizio ^{[9
]}

Spataro, Rossella ^{[10
]}

Schymick, Jennifer ^{[11
]}

Traynor, Bryan J. ^{[11
]}

La Bella, Vincenzo ^{[10
]}

机构：

[1] Univ Turin, ALS Ctr, Dept Neurosci, I-10126 Turin, Italy

[2] OIRM S Anna, ASO, Dept Clin Pathol, Mol Genet Unit, Turin, Italy

[3] Salvatore Maugeri Fdn, ALS Ctr, Milan, Italy

[4] Catholic Univ, Neurol Inst, Rome, Italy

[5] ICOMM Assoc ALS Res, Rome, Italy

[6] Univ Naples 2, Dept Neurol Sci, Naples, Italy

[7] Univ Siena, Neurol Sect, Dept Neurosci, I-53100 Siena, Italy

[8] Univ Modena, I-41100 Modena, Italy

[9] Bellaria Hosp, Dept Neurol, Ctr Diag & Cure Rare Dis, Bologna, Italy

[10] Univ Palermo, Dept Clin Neurosci, I-90133 Palermo, Italy

[11] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

来源：

NEUROBIOLOGY OF AGING | 2009年 / 30卷 / 08期

关键词：

Amyotrophic lateral sclerosis; Genetics; FUS gene; Family pedigrees; GENE;

D O I：

10.1016/j.neurobiolaging.2009.05.001

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：

Recently, fused in sarcoma/translated in liposarcoma (FUS/TLS) gene, located on chromosome 16p11.2, has been identified as a disease gene in familial amyotrophic lateral sclerosis (FALS). We have analyzed FUS/TLS in a cohort of 52 index cases from seven Italian regions with non-SOD1 and non-TARDBP FALS. We identified a heterozygous c.G1542C missense mutation in a family of northern Italian origin, and a heterozygous c.C1574T missense mutation in a family of Sicilian origin. Both variants are located in exon 15 encoding the RNA-recognition motif, and result in a substitution of an arginine with a serine in position 514 (p.R514S) and substitution of a proline with a leucine at position 525 (p.P525L), respectively. Overall, the two mutations accounted for 3.8% of 52 non-SOD1 and non-TDP43 index cases of FALS. The clinical phenotype was similar within each of the families, with a predominantly upper limb onset in the family carrying the p.R514S mutation and bulbar onset, with very young age and a rapid course in the family carrying the p.P525L mutation. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：1272 / 1275

页数：4

共 6 条

[1] El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis [J].

Brooks, BR ;

Miller, RG ;

Swash, M ;

Munsat, TL .

AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS, 2000, 1 (05) :293-299

[2] Prevalence of SOD1 mutations in the Italian ALS population [J].

Chio, A. ;

Traynor, B. J. ;

Lombardo, F. ;

Fimognari, M. ;

Calvo, A. ;

Ghiglione, P. ;

Mutani, R. ;

Restagno, G. .

NEUROLOGY, 2008, 70 (07) :533-537

[3] Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis [J].

Kwiatkowski, T. J., Jr. ;

Bosco, D. A. ;

LeClerc, A. L. ;

Tamrazian, E. ;

Vanderburg, C. R. ;

Russ, C. ;

Davis, A. ;

Gilchrist, J. ;

Kasarskis, E. J. ;

Munsat, T. ;

Valdmanis, P. ;

Rouleau, G. A. ;

Hosler, B. A. ;

Cortelli, P. ;

de Jong, P. J. ;

Yoshinaga, Y. ;

Haines, J. L. ;

Pericak-Vance, M. A. ;

Yan, J. ;

Ticozzi, N. ;

Siddique, T. ;

McKenna-Yasek, D. ;

Sapp, P. C. ;

Horvitz, H. R. ;

Landers, J. E. ;

Brown, R. H., Jr. .

SCIENCE, 2009, 323 (5918) :1205-1208

[4] MUTATIONS IN CU/ZN SUPEROXIDE-DISMUTASE GENE ARE ASSOCIATED WITH FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS [J].

ROSEN, DR ;

SIDDIQUE, T ;

PATTERSON, D ;

FIGLEWICZ, DA ;

SAPP, P ;

HENTATI, A ;

DONALDSON, D ;

GOTO, J ;

OREGAN, JP ;

DENG, HX ;

RAHMANI, Z ;

KRIZUS, A ;

MCKENNAYASEK, D ;

CAYABYAB, A ;

GASTON, SM ;

BERGER, R ;

TANZI, RE ;

HALPERIN, JJ ;

HERZFELDT, B ;

VANDENBERGH, R ;

HUNG, WY ;

BIRD, T ;

DENG, G ;

MULDER, DW ;

SMYTH, C ;

LAING, NG ;

SORIANO, E ;

PERICAKVANCE, MA ;

HAINES, J ;

ROULEAU, GA ;

GUSELLA, JS ;

HORVITZ, HR ;

BROWN, RH .

NATURE, 1993, 362 (6415) :59-62

[5] TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis [J].

Sreedharan, Jemeen ;

Blair, Ian P. ;

Tripathi, Vineeta B. ;

Hu, Xun ;

Vance, Caroline ;

Rogelj, Boris ;

Ackerley, Steven ;

Durnall, Jennifer C. ;

Williams, Kelly L. ;

Buratti, Emanuele ;

Baralle, Francisco ;

de Belleroche, Jacqueline ;

Mitchell, J. Douglas ;

Leigh, P. Nigel ;

Al-Chalabi, Ammar ;

Miller, Christopher C. ;

Nicholson, Garth ;

Shaw, Christopher E. .

SCIENCE, 2008, 319 (5870) :1668-1672

[6] Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6 [J].

Vance, Caroline ;

Rogelj, Boris ;

Hortobagyi, Tibor ;

De Vos, Kurt J. ;

Nishimura, Agnes Lumi ;

Sreedharan, Jemeen ;

Hu, Xun ;

Smith, Bradley ;

Ruddy, Deborah ;

Wright, Paul ;

Ganesalingam, Jeban ;

Williams, Kelly L. ;

Tripathi, Vineeta ;

Al-Saraj, Safa ;

Al-Chalabi, Ammar ;

Leigh, P. Nigel ;

Blair, Ian P. ;

Nicholson, Garth ;

de Belleroche, Jackie ;

Gallo, Jean-Marc ;

Miller, Christopher C. ;

Shaw, Christopher E. .

SCIENCE, 2009, 323 (5918) :1208-1211

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