BACKGROUND: An increasing number of dominant and recessive disorders have been associated with late onset chronic progressive ataxia (LOCA) complicating the formulation of a rational diagnostic strategy. Furthermore, there is marked geographic and ethnic variation in the relative importance of these individual disorders and the cause of such observed variation remains unexplained. METHODS: We have systematically investigated a population-based cohort of patients with chronic progressive LOCA for SCA 1, 2, 3, 6, 7, 8, 10, 12, 17, FXTAS and FRDA. In addition we have examined repeat length polymorphism in chromosomes from a genetically homogeneous and representative control population to investigate the association of high-normal repeats and disease prevalence. RESULTS: A total of 178 patients including 55 familial cases segregating in 38 kindreds and 123 sporadic were investigated. Pathological expansions were identified in 11/38 (28.9 %) of families and in 5/123 (4.1 %) of sporadic patients. The most frequent diagnoses were SCA6 (6 families and 1 sporadic patient), DRPLA (4 families) and SCA8 (1 family). In addition, one elderly female patient was identified with "possible FXTAS". Six (2 %) control patients were noted to have expanded SCA8 alleles. CONCLUSIONS: SCA6 and DRPLA were the most frequent genetic diagnoses identified. Patterns of high-normal allele frequency in this UK population were distinct compared to other ethnic groups but this was poorly predictive of the distribution of disease in this region. The relative contribution of new mutation formation and founder effects to the prevalence of familial ataxia is uncertain, and further exploration of these factors will require detailed analysis of disease allele haplotypes and meiotic instability of intermediate length alleles.
BACKGROUND: An increasing number of dominant and recessive disorders have been associated with late onset chronic progressive ataxia (LOCA) complicating the formulation of a rational diagnostic strategy. Furthermore, there is marked geographic and ethnic variation in the relative importance of these individual disorders and the cause of such observed variation remains unexplained. METHODS: We have systematically investigated a population-based cohort of patients with chronic progressive LOCA for SCA 1, 2, 3, 6, 7, 8, 10, 12, 17, FXTAS and FRDA. In addition we have examined repeat length polymorphism in chromosomes from a genetically homogeneous and representative control population to investigate the association of high-normal repeats and disease prevalence. RESULTS: A total of 178 patients including 55 familial cases segregating in 38 kindreds and 123 sporadic were investigated. Pathological expansions were identified in 11/38 (28.9 %) of families and in 5/123 (4.1 %) of sporadic patients. The most frequent diagnoses were SCA6 (6 families and 1 sporadic patient), DRPLA (4 families) and SCA8 (1 family). In addition, one elderly female patient was identified with "possible FXTAS". Six (2 %) control patients were noted to have expanded SCA8 alleles. CONCLUSIONS:SCA6 and DRPLA were the most frequent genetic diagnoses identified. Patterns of high-normal allele frequency in this UK population were distinct compared to other ethnic groups but this was poorly predictive of the distribution of disease in this region. The relative contribution of new mutation formation and founder effects to the prevalence of familial ataxia is uncertain, and further exploration of these factors will require detailed analysis of disease allele haplotypes and meiotic instability of intermediate length alleles.
Authors: M A Pujana; J Corral; M Gratacòs; O Combarros; J Berciano; D Genís; I Banchs; X Estivill; V Volpini Journal: Hum Genet Date: 1999-06 Impact factor: 4.132
Authors: U Nagaoka; Y Suzuki; T Kawanami; K Kurita; Y Shikama; K Honda; K Abe; T Nakajima; T Kato Journal: J Neurol Sci Date: 1999-04-01 Impact factor: 3.181
Authors: A Brussino; C Gellera; A Saluto; C Mariotti; C Arduino; B Castellotti; M Camerlingo; V de Angelis; L Orsi; P Tosca; N Migone; F Taroni; A Brusco Journal: Neurology Date: 2005-01-11 Impact factor: 9.910
Authors: E Majounie; M Wardle; M Muzaimi; W C Cross; N P Robertson; N M Williams; H R Morris Journal: Neurosci Lett Date: 2007-10-02 Impact factor: 3.046
Authors: Yoshio Ikeda; Joline C Dalton; Melinda L Moseley; Kathy L Gardner; Thomas D Bird; Tetsuo Ashizawa; William K Seltzer; Massimo Pandolfo; Aubrey Milunsky; Nicholas T Potter; Mikio Shoji; John B Vincent; John W Day; Laura P W Ranum Journal: Am J Hum Genet Date: 2004-05-19 Impact factor: 11.025
Authors: P Giunti; G Sabbadini; M G Sweeney; M B Davis; L Veneziano; E Mantuano; A Federico; R Plasmati; M Frontali; N W Wood Journal: Brain Date: 1998-03 Impact factor: 13.501
Authors: Adam M Staffaroni; Fanny M Elahi; Dana McDermott; Kacey Marton; Elissaios Karageorgiou; Simone Sacco; Matteo Paoletti; Eduardo Caverzasi; Christopher P Hess; Howard J Rosen; Michael D Geschwind Journal: Semin Neurol Date: 2017-12-05 Impact factor: 3.420
Authors: Ana I Seixas; José Vale; Paula Jorge; Isabel Marques; Rosário Santos; Isabel Alonso; Ana M Fortuna; Jorge Pinto-Basto; Paula Coutinho; Russell L Margolis; Jorge Sequeiros; Isabel Silveira Journal: Behav Brain Funct Date: 2011-06-03 Impact factor: 3.759
Authors: Esther B E Becker; Luigi Zuliani; Rosemary Pettingill; Bethan Lang; Patrick Waters; Anna Dulneva; Frank Sobott; Mark Wardle; Francesc Graus; Luis Bataller; Neil P Robertson; Angela Vincent Journal: J Neurol Neurosurg Psychiatry Date: 2012-02-15 Impact factor: 10.154