OBJECTIVE: Given the recent finding of an association between intermediate-length polyglutamine (polyQ) expansions in ataxin 2 and amyotrophic lateral sclerosis (ALS), we sought to determine whether expansions in other polyQ disease genes were associated with ALS. METHODS: We assessed the polyQ lengths of ataxin 1, ataxin 3, ataxin 6, ataxin 7, TBP, atrophin 1, and huntingtin in several hundred patients with sporadic ALS and healthy controls. RESULTS: Other than ataxin 2, we did not identify a significant association with the other polyQ genes and ALS. CONCLUSIONS: These data indicate that the effects of ataxin 2 polyQ expansions on ALS risk are likely to be rooted in the biology of ataxin 2 or ataxin 2-specific interactions, rather than the presence of an expanded polyQ repeat per se. These findings have important consequences for understanding the role of ataxin 2 in ALS pathogenesis and provide a framework for future mechanistic studies.
OBJECTIVE: Given the recent finding of an association between intermediate-length polyglutamine (polyQ) expansions in ataxin 2 and amyotrophic lateral sclerosis (ALS), we sought to determine whether expansions in other polyQ disease genes were associated with ALS. METHODS: We assessed the polyQ lengths of ataxin 1, ataxin 3, ataxin 6, ataxin 7, TBP, atrophin 1, and huntingtin in several hundred patients with sporadic ALS and healthy controls. RESULTS: Other than ataxin 2, we did not identify a significant association with the other polyQ genes and ALS. CONCLUSIONS: These data indicate that the effects of ataxin 2polyQ expansions on ALS risk are likely to be rooted in the biology of ataxin 2 or ataxin 2-specific interactions, rather than the presence of an expanded polyQ repeat per se. These findings have important consequences for understanding the role of ataxin 2 in ALS pathogenesis and provide a framework for future mechanistic studies.
Authors: S M Pulst; A Nechiporuk; T Nechiporuk; S Gispert; X N Chen; I Lopes-Cendes; S Pearlman; S Starkman; G Orozco-Diaz; A Lunkes; P DeJong; G A Rouleau; G Auburger; J R Korenberg; C Figueroa; S Sahba Journal: Nat Genet Date: 1996-11 Impact factor: 38.330
Authors: O Garofalo; D A Figlewicz; P N Leigh; J F Powell; V Meininger; M Dib; G A Rouleau Journal: Neuromuscul Disord Date: 1993-05 Impact factor: 4.296
Authors: Mari Tada; Elizabeth A Coon; Alexander P Osmand; Patricia A Kirby; Wayne Martin; Marguerite Wieler; Atsushi Shiga; Hiroe Shirasaki; Masayoshi Tada; Takao Makifuchi; Mitsunori Yamada; Akiyoshi Kakita; Masatoyo Nishizawa; Hitoshi Takahashi; Henry L Paulson Journal: Acta Neuropathol Date: 2012-06-27 Impact factor: 17.088
Authors: Amber Tariq; JiaBei Lin; Megan M Noll; Mariana P Torrente; Korrie L Mack; Oscar Hernandez Murillo; Meredith E Jackrel; James Shorter Journal: FEMS Yeast Res Date: 2018-08-01 Impact factor: 2.796
Authors: Mercedes Prudencio; Hector Garcia-Moreno; Karen R Jansen-West; Rana Hanna Al-Shaikh; Tania F Gendron; Michael G Heckman; Matthew R Spiegel; Yari Carlomagno; Lillian M Daughrity; Yuping Song; Judith A Dunmore; Natalie Byron; Björn Oskarsson; Katharine A Nicholson; Nathan P Staff; Sorina Gorcenco; Andreas Puschmann; João Lemos; Cristina Januário; Mark S LeDoux; Joseph H Friedman; James Polke; Robin Labrum; Vikram Shakkottai; Hayley S McLoughlin; Henry L Paulson; Takuya Konno; Osamu Onodera; Takeshi Ikeuchi; Mari Tada; Akiyoshi Kakita; John D Fryer; Christin Karremo; Inês Gomes; John N Caviness; Mark R Pittelkow; Jan Aasly; Ronald F Pfeiffer; Venka Veerappan; Eric R Eggenberger; William D Freeman; Josephine F Huang; Ryan J Uitti; Klaas J Wierenga; Iris V Marin Collazo; Philip W Tipton; Jay A van Gerpen; Marka van Blitterswijk; Guojun Bu; Zbigniew K Wszolek; Paola Giunti; Leonard Petrucelli Journal: Sci Transl Med Date: 2020-10-21 Impact factor: 17.956