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

Chiò, Adriano; Restagno, Gabriella; Brunetti, Maura; Ossola, Irene; Calvo, Andrea; Mora, Gabriele; Sabatelli, Mario; Monsurrò, Maria Rosaria; Battistini, Stefania; Mandrioli, Jessica; Salvi, Fabrizio; Spataro, Rossella; Schymick, Jennifer; Traynor, Bryan J.; La Bella, Vincenzo; the ITALSGEN Consortium,

doi:10.1016/j.neurobiolaging.2009.05.001

« Previous Next »Neurobiology of Aging
Volume 30, Issue 8 , Pages 1272-1275, August 2009

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

Adriano Chiò
- ALS Center, Department of Neuroscience, University of Turin, Via Cherasco 15, 10126 Turin, Italy
- These authors contributed equally to this work.
- Corresponding author. Tel.: +39 0116335439; fax: +39 0116963487.
Gabriella Restagno
- Molecular Genetics Unit, Department of Clinical Pathology, ASO, O.I.R.M.-S.Anna, Turin, Italy
- These authors contributed equally to this work.
Maura Brunetti
- Molecular Genetics Unit, Department of Clinical Pathology, ASO, O.I.R.M.-S.Anna, Turin, Italy
Irene Ossola
- Molecular Genetics Unit, Department of Clinical Pathology, ASO, O.I.R.M.-S.Anna, Turin, Italy
Andrea Calvo
- ALS Center, Department of Neuroscience, University of Turin, Via Cherasco 15, 10126 Turin, Italy
Gabriele Mora
- ALS Center, Salvatore Maugeri Foundation, Milano, Italy
Mario Sabatelli
- Neurological Institute, Catholic University and I.CO.M.M. Association for ALS Research, Rome, Italy
Maria Rosaria Monsurrò
- Department of Neurological Sciences, Second University of Naples, Italy
Stefania Battistini
- Department of Neuroscience, Neurology Section, University of Siena, Siena, Italy
Jessica Mandrioli
- Department of Neuroscience, S. Agostino-Estense Hospital, and University of Modena, Italy
Fabrizio Salvi
- Center for Diagnosis and Cure of Rare Diseases, Department of Neurology, Bellaria Hospital, Bologna, Italy
Rossella Spataro
- Department of Clinical Neurosciences, University of Palermo, Italy
Jennifer Schymick
- Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD, USA
Bryan J. Traynor
- Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD, USA
Vincenzo La Bella
- Department of Clinical Neurosciences, University of Palermo, Italy
the ITALSGEN Consortium
- See Appendix A for the other members of ITALSGEN.

Received 29 April 2009; accepted 1 May 2009. published online 18 May 2009.

Abstract

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.

Keywords: Amyotrophic lateral sclerosis, Genetics, FUS gene, Family pedigrees