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.

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

CHIO', Adriano;BRUNETTI, Maura;CALVO, Andrea;MOGLIA, CRISTINA;CAMMAROSANO, Stefania;
2009-01-01

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.
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amyotrophic lateral sclerosis; genetics
Chiò A; Restagno G; Brunetti M; Ossola I; Calvo A; Mora G; Sabatelli M; Monsurrò MR; Battistini S; Mandrioli J; Salvi F; Spataro R; Schymick J; Traynor BJ; La Bella V; Giannini F; Ricci C; Moglia C; Lombardo F; Sbaiz L; Cammarosano S; Tedeschi G; Sola P; Bartolomei I; Marinou K; Papetti L; Conte A; Luigetti M; Paladino P; Caponnetto C; Siciliano G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/60989
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