Clinical and molecular features of spinocerebellar ataxia type 6

Neurology ◽  
1997 ◽  
Vol 49 (5) ◽  
pp. 1243-1246 ◽  
Author(s):  
G. Stevanin ◽  
A. Dürr ◽  
G. David ◽  
O. Didierjean ◽  
G. Cancel ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Spinocerebellar Ataxia ◽  
Age At Onset ◽  
Cerebellar Atrophy ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Spinocerebellar Ataxia Type ◽  
Olivopontocerebellar Atrophy ◽  
Molecular Features ◽  
Spinocerebellar Ataxia Type 6

The mutation involved in spinocerebellar ataxia type 6 (SCA6) is a small CAG expansion in the alpha-1A subunit of the voltage-dependent calcium channel gene. We looked for this mutation in 91 families with autosomal-dominant cerebellar ataxias and found that SCA6 is a minor locus in our series (2%) and is rare in France (1%). Furthermore, we did not detect the SCA6 mutation on 146 sporadic cases with isolated cerebellar ataxia or olivopontocerebellar atrophy. The normal and expanded alleles ranged from 4 to 15 and 22 to 28 CAG repeats, respectively, and age at onset was correlated to CAG repeat length (r = -0.87). In contrast with other SCA, the expanded allele was stable during transmission. Clinically, SCA6 patients (n = 12) presented with moderate to severe cerebellar ataxia with a lower frequency of associated signs compared with other SCA and a mean age at onset of 45± 14 years (range, 24 to 67). MRI showed extensive cerebellar atrophy but not of the brainstem or cerebral cortex.

Spinocerebellar ataxia type 6

Neurology ◽  
1997 ◽  
Vol 49 (5) ◽  
pp. 1238-1243 ◽  
Author(s):  
R. Matsumura ◽  
N. Futamura ◽  
Y. Fujimoto ◽  
S. Yanagimoto ◽  
H. Horikawa ◽  
...  
Keyword(s):  
Family History ◽  
Cerebellar Ataxia ◽  
Age At Onset ◽  
Repeat Expansion ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Spinocerebellar Ataxia Type ◽  
Cag Repeat Expansion ◽  
Spinocerebellar Ataxia Type 6

Spinocerebellar ataxia type 6 (SCA6) is a newly classified autosomal-dominant cerebellar ataxia (ADCA) associated with CAG repeat expansion. We screened 111 patients with cerebellar ataxia for the SCA6 mutation. Of these, 35 patients were found to have expanded CAG repeats in the SCA6 gene, indicating that second to SCA3, SCA6 is the most common ADCA in Japan. Expanded alleles ranged from 21 to 29 repeats, whereas normal alleles had seven to 17 repeats. There was no change in the CAG repeat length during meiosis. The age at onset was inversely correlated with the repeat length. The main clinical feature of the 35 patients with SCA6 was slowly progressive cerebellar ataxia; multisystem involvement was not common. The 35 patients included nine cases without apparent family history of cerebellar ataxia. The sporadic cases had smaller CAG repeats (21 or 22 repeats) and a later age at onset (64.9 ± 4.9 years) than the other cases with established family history. We also identified one patient who was homozygous for the SCA6 repeat expansion. The homozygote showed an earlier age of onset and more severe clinical manifestations than her sister, a heterozygote carrying an expanded allele with the same repeat length as the homozygote. This finding suggests that the dosage of the CAG repeat expansion plays an important role in phenotypic expression in SCA6.

scholarly journals Spinocerebellar ataxia type 6 in Brazil

2008 ◽  
Vol 66 (3b) ◽  
pp. 691-694 ◽  
Author(s):  
Hélio A.G. Teive ◽  
Renato Puppi Munhoz ◽  
Salmo Raskin ◽  
Lineu César Werneck
Keyword(s):  
Cerebellar Ataxia ◽  
Spinocerebellar Ataxia ◽  
Late Onset ◽  
Cag Repeat ◽  
Autosomal Dominant Cerebellar Ataxia ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 6 ◽  
Voltage Dependent ◽  
Pure Cerebellar Ataxia ◽  
Japanese Ancestry

Spinocerebellar ataxia type 6 (SCA 6) is an autosomal dominant cerebellar ataxia caused by CAG repeat expansion in the SCA6 gene, a alpha 1A voltage-dependent calcium channel subunit gene on chromosome 19p13. SCA-6 is characterized predominantly by slowly progressive pure cerebellar ataxia with late onset. We report three index patients, with pure, late onset, cerebellar ataxia, belonging to three different Brazilian families, all of them with Japanese ancestry, from Hokkaido island of Japan.

Bovine CACNA1A gene and comparative analysis of the CAG repeats associated to human spinocerebellar ataxia type-6

Gene ◽  
2006 ◽  
Vol 380 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Eva Andrés-Mateos ◽  
Jesús Cruces ◽  
Jaime Renart ◽  
Luisa M. Solís-Garrido ◽  
Rocío Serantes ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Spinocerebellar Ataxia ◽  
Cag Repeats ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 6 ◽  
Cacna1a Gene

scholarly journals Homozygous spinocerebellar ataxia type 3 in China: a case report

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110213
Author(s):  
Yuchao Chen ◽  
Dan Li ◽  
Minger Wei ◽  
Menglu Zhou ◽  
Linan Zhang ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Clinical Phenotype ◽  
Gene Dosage ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Spinocerebellar Ataxia Type ◽  
Contraction Pattern ◽  
Spinocerebellar Ataxia Type 3 ◽  
Type 3 ◽  
Stable Transmission

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease caused by a heterozygous CAG repeat expansion in the ataxin 3 gene ( ATXN3). However, patients with homozygous SCA3 carrying expanded CAG repeats in both alleles of ATXN3 are extremely rare. Herein, we present a case of a 50-year-old female who had homozygous SCA3 with expansion of 62/62 repeats. Segregation analysis of the patient’s family showed both a contraction pattern of CAG repeat length and stable transmission. The present case demonstrated an earlier onset and more severe clinical phenotype than that seen in heterozygous individuals, suggesting that the gene dosage enhances disease severity.

Spinocerebellar ataxia type 6 in relation to CAG repeat length

1999 ◽  
Vol 99 (4) ◽  
pp. 209-212 ◽  
Author(s):  
Y. Kaseda ◽  
H. Kawakami ◽  
Z. Matsuyama ◽  
R. Kumagai ◽  
M. Toji ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Repeat Length ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 6

scholarly journals Genetic analysis of age at onset variation in spinocerebellar ataxia type 2

2017 ◽  
Vol 3 (3) ◽  
pp. e155 ◽  
Author(s):  
K.P. Figueroa ◽  
Hilary Coon ◽  
Nieves Santos ◽  
Luis Velazquez ◽  
Luis Almaguer Mederos ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Age At Onset ◽  
Repeat Length ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Spinocerebellar Ataxia Type 2 ◽  
Entire Sample ◽  
Sib Pairs ◽  
Parent Child

Objective:To examine heritability of the residual variability of spinocerebellar ataxia type 2 (SCA2) age at onset (AO) after controlling for CAG repeat length.Methods:From 1955 to 2001, dates of birth, CAG repeat lengths, AO, sex, familial inheritances, and clinical manifestations were collected for a large Cuban SCA2 cohort of 382 affected individuals, including 129 parent-child pairs and 69 sibships. Analyses were performed with log-transformed AO in the GENMOD procedure to predict AO using repeat length, taking into account family structure. Because all relationships were first degree, the model was implemented with an exchangeable correlation matrix. Familial correlations were estimated using the Pedigree Analysis Package to control for similarity due to genetic relatedness.Results:For the entire sample, the mutant CAG repeat allele explained 69% of AO variance. When adjusted for pedigree structure, this decreased to 50%. Evidence for imprinting or sex-specific effects of the CAG repeat on AO was not found. For the entire sample, we determined an upper bound for heritability of the residual variance of 33% (p = 0.008). Heritability was higher in sib-sib pairs, especially in female sib-sib pairs, than in parent-child pairs.Conclusions:We established that a large proportion of AO variance in SCA2 was determined by genetic modifiers in addition to CAG repeat length. The genetic structure of heritability of the residual AO variance was surprisingly similar to Huntington disease, suggesting the presence of recessive modifying alleles and possibly X-chromosome–linked modifiers.

Meiotic CAG repeat instability in spinocerebellar ataxia type 6: Maternally transmitted elongation in a presumed sporadic case

2006 ◽  
Vol 241 (1-2) ◽  
pp. 95-98 ◽  
Author(s):  
Suzanne Granhøj Lindquist ◽  
Anne Nørremølle ◽  
Lena Elisabeth Hjermind ◽  
Lis Hasholt ◽  
Jørgen Erik Nielsen
Keyword(s):  
Spinocerebellar Ataxia ◽  
Sporadic Case ◽  
Cag Repeat ◽  
Spinocerebellar Ataxia Type ◽  
Repeat Instability ◽  
Spinocerebellar Ataxia Type 6
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