Are (CTG)n expansions at the SCA8 locus rare polymorphisms?

Stevanin, Giovanni; Herman, Alexandra; Dürr, Alexandra; Jodice, Carla; Frontali, Marina; Agid, Yves; Brice, Alexis

doi:10.1038/73408

Cited by 80 publications

(69 citation statements)

References 9 publications

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“…Several authors have reported the segregation of alleles > 85 triplets in familial ataxia patients, where their frequency (3-13 %) seems to far exceed that found in normal subjects (0.5-0.7 %) [8,19,20,26]. This is also true for our survey, where two out of 46 ataxic families carry an expansion in the gene (4.3 %), whereas no allele > 35 repeats was found among 127 controls with no ataxia.Although this difference is not statistically significant, the apparent clustering of SCA8 expansions among familial cases seems to support its pathogenetic role.…”

Section: Discussionmentioning

confidence: 95%

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Analysis of SCA8 and SCA12 loci in 134 Italian ataxic patients negative for SCA1-3, 6 and 7 CAG expansions

Brusco¹,

Cagnoli²,

Franco

et al. 2002

Journal of Neurology

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Spinocerebellar ataxias (SCA) are a heterogeneous group of neurodegenerative disorders, six of which are caused by expansion of a polyglutamine-coding CAG repeats ( SCA1- 3, 6, 7 and 17). In addition, expansions of a CAG triplet in the 5' region of a gene and a CTG triplet in an antisense RNA have been demonstrated in the SCA12 and SCA8 genes respectively. Our series of 134 ataxic patients (22 familial and 112 sporadic, tested negative for SCAI-3, 6, 7) was investigated for the presence of triplet expansions in the SCA8 and SCA12 genes. No SCA12 expansion was identified. A moderate SCA8 expansion (85-97 repeats) was found in two unrelated families with slowly progressive cerebellar ataxia. The frequency of SCA8 expansion accounts for approximately 4.3 % of the whole pool of our ataxia families (2 out of 46), while none of the 127 controls screened carried > 35 CTG+CTA repeats. Our data suggest a possible pathogenetic role of this mutation, which at present is still controversial, and confirm the rarity of the SCA12 expansion in Italian patients.

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Section: Discussionmentioning

confidence: 95%

“…s Key words SCA · Spinocerebellar ataxia · CAG repeat · polyglutamines thermore expanded alleles were also found among healthy subjects [20,24,26]. The role of the SCA8 expansion is therefore still controversial.…”

mentioning

confidence: 98%

Analysis of SCA8 and SCA12 loci in 134 Italian ataxic patients negative for SCA1-3, 6 and 7 CAG expansions

Brusco¹,

Cagnoli²,

Franco

et al. 2002

Journal of Neurology

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“…Interestingly, MRI analysis of one clinically unaffected carrier (age 71) with 136 combined repeats revealed mild atrophy of the cerebellar hemispheres (Ikeda et al, 2000b). Surprisingly, SCA8 expansions 1100 combined repeats have also been found among control chromosomes at a frequency of F1/1,000, leading some to suggest the possibility that a separate mutation in linkage disequilibrium could exist among ataxia patients but not controls (Stevanin et al, 2000;Vincent et al, 2000;Worth et al, 2000).…”

Section: Reduced Penetrance In Other Familiesmentioning

confidence: 99%

“…Among the larger group of families we have studied, the repeat sizes most often associated with ataxia range from 80 to 250 combined CTA/CTG repeats; however, repeat sizes ranging from 71 to over 1,000 repeats have been found in some individuals with ataxia. Further analysis of other families showed that the pathogenic size range of the SCA8 expansion can vary between families and that a positive test for an SCA8 expansion cannot be used to predict whether or not an asymptomatic individual will develop ataxia, regardless of repeat size Ranum et al, 1999;Day et al, 2000;Juvonen et al, 2000;Moseley et al, 2000b;Stevanin et al, 2000;Worth et al, 2000;Sobrido et al, 2001). Interestingly, MRI analysis of one clinically unaffected carrier (age 71) with 136 combined repeats revealed mild atrophy of the cerebellar hemispheres (Ikeda et al, 2000b).…”

Section: Reduced Penetrance In Other Familiesmentioning

confidence: 99%

Molecular genetics of spinocerebellar ataxia type 8 (SCA8)

Mosemiller

Dalton

Day

et al. 2003

Cytogenet Genome Res

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We previously reported that a transcribed but untranslated CTG expansion causes a novel form of ataxia, spinocerebellar ataxia type 8 (SCA8) (Koob et al., 1999). SCA8 was the first example of a dominant spinocerebellar ataxia that is not caused by the expansion of a CAG repeat translated into a polyglutamine tract. This slowly progressive form of ataxia is characterized by dramatic repeat instability and a high degree of reduced penetrance. The clinical and genetic features of the disease are discussed below.

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“…Further studies have reported a number of healthy controls and elderly unaffected family members who do not have ataxia but nevertheless have large expansions at the gene locus [3][4][5][6][7]. We describe a mother and son with the SCA8 expansion with executive, visuospatial and affective problems in addition to an ataxic syndrome.…”

mentioning

confidence: 96%