BACKGROUND AND PURPOSE: Increasing evidence suggests a direct role of the TAR DNA-binding protein 43 (TDP-43) in neurodegeneration. Mutations in the TARDBP gene, which codes for TDP-43, have been recently reported in familial and sporadic amyotrophic lateral sclerosis (ALS) cases. METHODS: To further define the spectrum and frequency of TARDBP mutations, we present genetic analysis data on TARDBP in 314 ALS mainly Italian patients, including 16 subjects with non-SOD1 familial ALS. RESULTS: We identified four heterozygous missense mutations in five unrelated ALS patients (1.6%). Two of these mutations (p.G348C and p.A382T) were detected in carriers coming from families with an autosomal dominant transmission of different geographic origin (Belgian and Italian, respectively). The Belgian pedigree showed several affected members within five generations and with variable clinical features. Two novel mutations (p.G294V and p.G295S) were identified in two sporadic cases. CONCLUSION: The identification of five ALS patients carrying TARDBP alterations extends the spectrum of TARDBP mutations and supports the pathological role of TDP-43 in motor neurone disease. Our findings provide evidence that TARDBP mutations are not frequent in Italian sporadic ALS patients (1%); however, combined with the literature, our data further support TARDBP mutations as a relevant cause of familial ALS.
BACKGROUND AND PURPOSE: Increasing evidence suggests a direct role of the TAR DNA-binding protein 43 (TDP-43) in neurodegeneration. Mutations in the TARDBP gene, which codes for TDP-43, have been recently reported in familial and sporadic amyotrophic lateral sclerosis (ALS) cases. METHODS: To further define the spectrum and frequency of TARDBP mutations, we present genetic analysis data on TARDBP in 314 ALS mainly Italian patients, including 16 subjects with non-SOD1familial ALS. RESULTS: We identified four heterozygous missense mutations in five unrelated ALSpatients (1.6%). Two of these mutations (p.G348C and p.A382T) were detected in carriers coming from families with an autosomal dominant transmission of different geographic origin (Belgian and Italian, respectively). The Belgian pedigree showed several affected members within five generations and with variable clinical features. Two novel mutations (p.G294V and p.G295S) were identified in two sporadic cases. CONCLUSION: The identification of five ALSpatients carrying TARDBP alterations extends the spectrum of TARDBP mutations and supports the pathological role of TDP-43 in motor neurone disease. Our findings provide evidence that TARDBP mutations are not frequent in Italian sporadic ALSpatients (1%); however, combined with the literature, our data further support TARDBP mutations as a relevant cause of familial ALS.
Authors: Colleen M Dewey; Basar Cenik; Chantelle F Sephton; Brett A Johnson; Joachim Herz; Gang Yu Journal: Brain Res Date: 2012-02-22 Impact factor: 3.252
Authors: Adriano Chiò; Giuseppe Borghero; Maura Pugliatti; Anna Ticca; Andrea Calvo; Cristina Moglia; Roberto Mutani; Maura Brunetti; Irene Ossola; Maria Giovanna Marrosu; Maria Rita Murru; Gianluca Floris; Antonino Cannas; Leslie D Parish; Paola Cossu; Yevgeniya Abramzon; Janel O Johnson; Michael A Nalls; Sampath Arepalli; Sean Chong; Dena G Hernandez; Bryan J Traynor; Gabriella Restagno Journal: Arch Neurol Date: 2011-01-10
Authors: Erika N Guerrero; Haibo Wang; Joy Mitra; Pavana M Hegde; Sara E Stowell; Nicole F Liachko; Brian C Kraemer; Ralph M Garruto; K S Rao; Muralidhar L Hegde Journal: Prog Neurobiol Date: 2016-09-28 Impact factor: 11.685
Authors: Janine Kirby; Emily F Goodall; William Smith; J Robin Highley; Rudo Masanzu; Judith A Hartley; Rachel Hibberd; Hannah C Hollinger; Stephen B Wharton; Karen E Morrison; Paul G Ince; Christopher J McDermott; Pamela J Shaw Journal: Neurogenetics Date: 2009-09-17 Impact factor: 2.660