BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia (ADCA) for which the disease-causing mutation has recently been characterized as an expanded CAG trinucleotide repeat. We investigated 64 families of German ancestry with ADCA and 55 patients with sporadic ataxia for the SCA2 mutation. RESULTS: Expanded alleles were found in 6 of the 64 families and in 1 patient with sporadic ataxia. This patient had a de novo mutation from an intermediate paternal allele. Length of repeats in 21 patients with SCA2 ranged from 36 to 52 CAG motifs and was inversely correlated with age at onset and progression of the disease. Expanded alleles were unstable during meiosis; paternal transmission especially caused significant anticipation of onset up to 26 years earlier. The SCA2 phenotype differed from those of SCA1 and SCA3 with higher frequencies of slowed ocular movements, postural and action tremor, myoclonus, and hyporeflexia. However, no single feature was sufficient to permit a specific clinical diagnosis. CONCLUSIONS: Spinocerebellar ataxia type 2 accounts for about 10% of German families with ADCA but may also be present in sporadic ataxia due to de novo mutations. Clinical features are highly variable among and even within families. However, the size of the expanded repeat influences the phenotype and is relevant for course and prognosis of the disease.
BACKGROUND:Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant cerebellar ataxia (ADCA) for which the disease-causing mutation has recently been characterized as an expanded CAGtrinucleotide repeat. We investigated 64 families of German ancestry with ADCA and 55 patients with sporadic ataxia for the SCA2 mutation. RESULTS: Expanded alleles were found in 6 of the 64 families and in 1 patient with sporadic ataxia. This patient had a de novo mutation from an intermediate paternal allele. Length of repeats in 21 patients with SCA2 ranged from 36 to 52 CAG motifs and was inversely correlated with age at onset and progression of the disease. Expanded alleles were unstable during meiosis; paternal transmission especially caused significant anticipation of onset up to 26 years earlier. The SCA2 phenotype differed from those of SCA1 and SCA3 with higher frequencies of slowed ocular movements, postural and action tremor, myoclonus, and hyporeflexia. However, no single feature was sufficient to permit a specific clinical diagnosis. CONCLUSIONS:Spinocerebellar ataxia type 2 accounts for about 10% of German families with ADCA but may also be present in sporadic ataxia due to de novo mutations. Clinical features are highly variable among and even within families. However, the size of the expanded repeat influences the phenotype and is relevant for course and prognosis of the disease.
Authors: H Jacobi; P Bauer; P Giunti; R Labrum; M G Sweeney; P Charles; A Dürr; C Marelli; C Globas; C Linnemann; L Schöls; M Rakowicz; R Rola; E Zdzienicka; T Schmitz-Hübsch; R Fancellu; C Mariotti; C Tomasello; L Baliko; B Melegh; A Filla; C Rinaldi; B P van de Warrenburg; C C P Verstappen; S Szymanski; J Berciano; J Infante; D Timmann; S Boesch; S Hering; C Depondt; M Pandolfo; J-S Kang; S Ratzka; J Schulz; S Tezenas du Montcel; T Klockgether Journal: Neurology Date: 2011-08-10 Impact factor: 9.910
Authors: Heike Jacobi; Till-Karsten Hauser; Paola Giunti; Christoph Globas; Peter Bauer; Tanja Schmitz-Hübsch; László Baliko; Alessandro Filla; Caterina Mariotti; Maria Rakowicz; Perine Charles; Pascale Ribai; Sandra Szymanski; Jon Infante; Bart P C van de Warrenburg; Alexandra Dürr; Dagmar Timmann; Sylvia Boesch; Roberto Fancellu; Rafal Rola; Chantal Depondt; Ludger Schöls; Elzbieta Zdzienicka; Jun-Suk Kang; Susanne Ratzka; Berry Kremer; Dennis A Stephenson; Béla Melegh; Massimo Pandolfo; Sophie Tezenas du Montcel; Johannes Borkert; Jörg B Schulz; Thomas Klockgether Journal: Cerebellum Date: 2012-03 Impact factor: 3.847