OMIM: 105550Inheritance: Autosomal dominant
Classification: Diseases of the nervous system
Related informations: Orphanet Gene Tests Clinical Synopsis Clinical Trials| Gene/Locus: | C9ORF72 |
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| Dna Change: | (GGGGCC)n EXPANSION |
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| Protein Change: | |
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| Mutation Type: | Sequence repeat |
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| Mutation Effect: | |
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| Location: | exon 1 |
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| Transcript: | NM_145005.5 |
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| Population | Ethnic Group | Region | Mutation Frquency | Coalescence Time | Reference |
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| Italy | NA | NA | 20% | 6300 years ago | Smith BN et al., 2013Smith BN, Newhouse S, Shatunov A, Vance C, Topp S, Johnson L, Miller J, Lee Y, Troakes C, Scott KM, Jones A, Gray I, Wright J, Hortobágyi T, Al-Sarraj S, Rogelj B, Powell J, Lupton M, Lovestone S, Sapp PC, Weber M, Nestor PJ, Schelhaas HJ, Asbroek AA, Silani V, Gellera C, Taroni F, Ticozzi N, Van den Berg L, Veldink J, Van Damme P, Robberecht W, Shaw PJ, Kirby J, Pall H, Morrison KE, Morris A, de Belleroche J, Vianney de Jong JM, Baas F, Andersen PM, Landers J, Brown RH, Weale ME, Al-Chalabi A, Shaw CE, . The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder.. Eur. J. Hum. Genet.. 2013; 21(1):102-8 |
| Italy | NA | Sardinia | NA | NA | Chiò A et al., 2012Chiò A, Restagno G, Brunetti M, Ossola I, Calvo A, Canosa A, Moglia C, Floris G, Tacconi P, Marrosu F, Marrosu MG, Murru MR, Majounie E, Renton AE, Abramzon Y, Pugliatti M, Sotgiu MA, Traynor BJ, Borghero G, , . ALS/FTD phenotype in two Sardinian families carrying both C9ORF72 and TARDBP mutations.. J. Neurol. Neurosurg. Psychiatr.. 2012; 83(7):730-3 |
| Italy | NA | NA | 23.9% of patients with familial ALS (62/259 patients) | NA | Ratti A et al., 2012Ratti A, Corrado L, Castellotti B, Del Bo R, Fogh I, Cereda C, Tiloca C, D'Ascenzo C, Bagarotti A, Pensato V, Ranieri M, Gagliardi S, Calini D, Mazzini L, Taroni F, Corti S, Ceroni M, Oggioni GD, Lin K, Powell JF, Sorarù G, Ticozzi N, Comi GP, D'Alfonso S, Gellera C, Silani V, , . C9ORF72 repeat expansion in a large Italian ALS cohort: evidence of a founder effect.. Neurobiol. Aging. 2012; 33(10):2528.e7-14 |
| Spain | NA | NA | 8.2% (9 patients/109 patients) | NA | Gómez-Tortosa E et al., 2013Gómez-Tortosa E, Gallego J, Guerrero-López R, Marcos A, Gil-Neciga E, Sainz MJ, Díaz A, Franco-Macías E, Trujillo-Tiebas MJ, Ayuso C, Pérez-Pérez J, . C9ORF72 hexanucleotide expansions of 20-22 repeats are associated with frontotemporal deterioration.. Neurology. 2013; 80(4):366-70 |
| Gene/Locus: | TARDBP |
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| Dna Change: | c.1144G>A |
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| Protein Change: | p.Ala382Th |
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| Mutation Type: | Substitution |
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| Mutation Effect: | Missense |
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| Location: | exon 6 |
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| Transcript: | NM_007375.3 |
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| Population | Ethnic Group | Region | Mutation Frquency | Coalescence Time | Reference |
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| Italy | NA | Sardinia | NA | NA | Chiò A et al., 2012Chiò A, Restagno G, Brunetti M, Ossola I, Calvo A, Canosa A, Moglia C, Floris G, Tacconi P, Marrosu F, Marrosu MG, Murru MR, Majounie E, Renton AE, Abramzon Y, Pugliatti M, Sotgiu MA, Traynor BJ, Borghero G, , . ALS/FTD phenotype in two Sardinian families carrying both C9ORF72 and TARDBP mutations.. J. Neurol. Neurosurg. Psychiatr.. 2012; 83(7):730-3 |
| Italy | NA | Sardinia | 30.9% | NA | Orrù S et al., 2012Orrù S, Manolakos E, Orrù N, Kokotas H, Mascia V, Carcassi C, Petersen MB, . High frequency of the TARDBP p.Ala382Thr mutation in Sardinian patients with amyotrophic lateral sclerosis.. Clin. Genet.. 2012; 81(2):172-8 |
| Italy | NA | Sardinia | 28.7% (39 patients/135 patients) | NA | Chiò A et al., 2011Chiò A, Borghero G, Pugliatti M, Ticca A, Calvo A, Moglia C, Mutani R, Brunetti M, Ossola I, Marrosu MG, Murru MR, Floris G, Cannas A, Parish LD, Cossu P, Abramzon Y, Johnson JO, Nalls MA, Arepalli S, Chong S, Hernandez DG, Traynor BJ, Restagno G, , . Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene.. Arch. Neurol.. 2011; 68(5):594-8 |
| Italy | NA | NA | 7 patients/666 patients | NA | Corrado L et al., 2009Corrado L, Ratti A, Gellera C, Buratti E, Castellotti B, Carlomagno Y, Ticozzi N, Mazzini L, Testa L, Taroni F, Baralle FE, Silani V, D'Alfonso S, . High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis.. Hum. Mutat.. 2009; 30(4):688-94 |
References
Chiò A, Borghero G, Pugliatti M, Ticca A, Calvo A, Moglia C, Mutani R, Brunetti M, Ossola I, Marrosu MG, Murru MR, Floris G, Cannas A, Parish LD, Cossu P, Abramzon Y, Johnson JO, Nalls MA, Arepalli S, Chong S, Hernandez DG, Traynor BJ, Restagno G, , Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene.Arch. Neurol.. 2011; 68(5):594-8
Chiò A, Restagno G, Brunetti M, Ossola I, Calvo A, Canosa A, Moglia C, Floris G, Tacconi P, Marrosu F, Marrosu MG, Murru MR, Majounie E, Renton AE, Abramzon Y, Pugliatti M, Sotgiu MA, Traynor BJ, Borghero G, , ALS/FTD phenotype in two Sardinian families carrying both C9ORF72 and TARDBP mutations.J. Neurol. Neurosurg. Psychiatr.. 2012; 83(7):730-3
Corrado L, Ratti A, Gellera C, Buratti E, Castellotti B, Carlomagno Y, Ticozzi N, Mazzini L, Testa L, Taroni F, Baralle FE, Silani V, D'Alfonso S, High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis.Hum. Mutat.. 2009; 30(4):688-94
Gómez-Tortosa E, Gallego J, Guerrero-López R, Marcos A, Gil-Neciga E, Sainz MJ, Díaz A, Franco-Macías E, Trujillo-Tiebas MJ, Ayuso C, Pérez-Pérez J, C9ORF72 hexanucleotide expansions of 20-22 repeats are associated with frontotemporal deterioration.Neurology. 2013; 80(4):366-70
Orrù S, Manolakos E, Orrù N, Kokotas H, Mascia V, Carcassi C, Petersen MB, High frequency of the TARDBP p.Ala382Thr mutation in Sardinian patients with amyotrophic lateral sclerosis.Clin. Genet.. 2012; 81(2):172-8
Ratti A, Corrado L, Castellotti B, Del Bo R, Fogh I, Cereda C, Tiloca C, D'Ascenzo C, Bagarotti A, Pensato V, Ranieri M, Gagliardi S, Calini D, Mazzini L, Taroni F, Corti S, Ceroni M, Oggioni GD, Lin K, Powell JF, Sorarù G, Ticozzi N, Comi GP, D'Alfonso S, Gellera C, Silani V, , C9ORF72 repeat expansion in a large Italian ALS cohort: evidence of a founder effect.Neurobiol. Aging. 2012; 33(10):2528.e7-14
Smith BN, Newhouse S, Shatunov A, Vance C, Topp S, Johnson L, Miller J, Lee Y, Troakes C, Scott KM, Jones A, Gray I, Wright J, Hortobágyi T, Al-Sarraj S, Rogelj B, Powell J, Lupton M, Lovestone S, Sapp PC, Weber M, Nestor PJ, Schelhaas HJ, Asbroek AA, Silani V, Gellera C, Taroni F, Ticozzi N, Van den Berg L, Veldink J, Van Damme P, Robberecht W, Shaw PJ, Kirby J, Pall H, Morrison KE, Morris A, de Belleroche J, Vianney de Jong JM, Baas F, Andersen PM, Landers J, Brown RH, Weale ME, Al-Chalabi A, Shaw CE, The C9ORF72 expansion mutation is a common cause of ALS+/-FTD in Europe and has a single founder.Eur. J. Hum. Genet.. 2013; 21(1):102-8