Genetic and Clinical Analysis of Spinocerebellar Ataxia Type 8 Repeat Expansion in Italy

Abstract

Our data support the evidence that CTG expansions may be linked to SCA8, since the pathogenic expansions have been found only among patients with genetically unidentified forms of hereditary and sporadic ataxia. Patients carrying expanded alleles present peculiar phenotypic features, thus suggesting that unknown additional factors could probably predispose to the disease.

Clinical feature profile of spinocerebellar ataxia type 1–8 predicts genetically defined subtypes

“…The clinical findings of the present study are very similar to those reported in previous studies 7, 10, 15–29. In particular, slowed eye movements were shown to be characteristic for SCA2, whereas diplopia and nystagmus seem to determine the ocular motor syndrome of SCA3 10, 15, 17, 18.…”

“…Patients with SCA5 had very infrequently associated symptoms such as tingling and cramps, which could not be explained by cerebellar dysfunction and is in keeping with results of other studies 22. The finding that the cerebellar syndrome of SCA8 was combined with extracerebellar symptoms such as myoclonus or incontinence only in the minority of patients confirms results of previous studies 11, 23. In recent years, the diagnosis of SCA8 has been challenging owing to incomplete penetrance, and close attention to clinical setting and genetic criteria has been urged 10, 23–26.…”

“…The finding that the cerebellar syndrome of SCA8 was combined with extracerebellar symptoms such as myoclonus or incontinence only in the minority of patients confirms results of previous studies 11, 23. In recent years, the diagnosis of SCA8 has been challenging owing to incomplete penetrance, and close attention to clinical setting and genetic criteria has been urged 10, 23–26. The patients in this study had repeat lengths that were in the range of other studies and the expansion segregated with the disease in the familial cases 11, 24.…”

Clinical feature profile of spinocerebellar ataxia type 1–8 predicts genetically defined subtypes

“…The clinical findings of the present study are very similar to those reported in previous studies 7, 10, 15–29. In particular, slowed eye movements were shown to be characteristic for SCA2, whereas diplopia and nystagmus seem to determine the ocular motor syndrome of SCA3 10, 15, 17, 18.…”

“…Patients with SCA5 had very infrequently associated symptoms such as tingling and cramps, which could not be explained by cerebellar dysfunction and is in keeping with results of other studies 22. The finding that the cerebellar syndrome of SCA8 was combined with extracerebellar symptoms such as myoclonus or incontinence only in the minority of patients confirms results of previous studies 11, 23. In recent years, the diagnosis of SCA8 has been challenging owing to incomplete penetrance, and close attention to clinical setting and genetic criteria has been urged 10, 23–26.…”

“…The finding that the cerebellar syndrome of SCA8 was combined with extracerebellar symptoms such as myoclonus or incontinence only in the minority of patients confirms results of previous studies 11, 23. In recent years, the diagnosis of SCA8 has been challenging owing to incomplete penetrance, and close attention to clinical setting and genetic criteria has been urged 10, 23–26. The patients in this study had repeat lengths that were in the range of other studies and the expansion segregated with the disease in the familial cases 11, 24.…”

Analysis of trinucleotide repeats in different SCA loci in spinocerebellar ataxia patients and in normal population of Taiwan

“…Recently, Cellini et al (2001) reported that the CTA/CTG repeats in the SCA8 locus varied from 15 to 75 triplets among normal individuals (29). The distribution of normal alleles in this study was similar to that previously reported in other ethnic groups (13,29). The most frequent allele contained 28 repeats, accounting for 16% of all normal controls analyzed.…”

CCG•CGG interruptions in high‐penetrance SCA8 families increase RAN translation and protein toxicity

“…Interestingly, four of the sporadic and two familial cases are homozygous and have two expanded alleles. These data and previous reports of expansion alleles in unaffected family members and in the general population (Moseley et al , 2000a; Stevanin et al , 2000; Worth et al , 2000; Cellini et al , 2001; Ikeda et al , 2004; Zeman et al , 2004) highlight the need to understand the molecular basis of the variable penetrance found in SCA8.…”

Clinical feature profile of spinocerebellar ataxia type 1–8 predicts genetically defined subtypes

“…The clinical findings of the present study are very similar to those reported in previous studies 7, 10, 15–29. In particular, slowed eye movements were shown to be characteristic for SCA2, whereas diplopia and nystagmus seem to determine the ocular motor syndrome of SCA3 10, 15, 17, 18.…”

“…Patients with SCA5 had very infrequently associated symptoms such as tingling and cramps, which could not be explained by cerebellar dysfunction and is in keeping with results of other studies 22. The finding that the cerebellar syndrome of SCA8 was combined with extracerebellar symptoms such as myoclonus or incontinence only in the minority of patients confirms results of previous studies 11, 23. In recent years, the diagnosis of SCA8 has been challenging owing to incomplete penetrance, and close attention to clinical setting and genetic criteria has been urged 10, 23–26.…”

“…The finding that the cerebellar syndrome of SCA8 was combined with extracerebellar symptoms such as myoclonus or incontinence only in the minority of patients confirms results of previous studies 11, 23. In recent years, the diagnosis of SCA8 has been challenging owing to incomplete penetrance, and close attention to clinical setting and genetic criteria has been urged 10, 23–26. The patients in this study had repeat lengths that were in the range of other studies and the expansion segregated with the disease in the familial cases 11, 24.…”

Analysis of trinucleotide repeats in different SCA loci in spinocerebellar ataxia patients and in normal population of Taiwan

“…Recently, Cellini et al (2001) reported that the CTA/CTG repeats in the SCA8 locus varied from 15 to 75 triplets among normal individuals (29). The distribution of normal alleles in this study was similar to that previously reported in other ethnic groups (13,29). The most frequent allele contained 28 repeats, accounting for 16% of all normal controls analyzed.…”

CCG•CGG interruptions in high‐penetrance SCA8 families increase RAN translation and protein toxicity

“…Interestingly, four of the sporadic and two familial cases are homozygous and have two expanded alleles. These data and previous reports of expansion alleles in unaffected family members and in the general population (Moseley et al , 2000a; Stevanin et al , 2000; Worth et al , 2000; Cellini et al , 2001; Ikeda et al , 2004; Zeman et al , 2004) highlight the need to understand the molecular basis of the variable penetrance found in SCA8.…”

Clinical feature profile of spinocerebellar ataxia type 1–8 predicts genetically defined subtypes

“…The clinical findings of the present study are very similar to those reported in previous studies 7, 10, 15–29. In particular, slowed eye movements were shown to be characteristic for SCA2, whereas diplopia and nystagmus seem to determine the ocular motor syndrome of SCA3 10, 15, 17, 18.…”

“…Patients with SCA5 had very infrequently associated symptoms such as tingling and cramps, which could not be explained by cerebellar dysfunction and is in keeping with results of other studies 22. The finding that the cerebellar syndrome of SCA8 was combined with extracerebellar symptoms such as myoclonus or incontinence only in the minority of patients confirms results of previous studies 11, 23. In recent years, the diagnosis of SCA8 has been challenging owing to incomplete penetrance, and close attention to clinical setting and genetic criteria has been urged 10, 23–26.…”

“…The finding that the cerebellar syndrome of SCA8 was combined with extracerebellar symptoms such as myoclonus or incontinence only in the minority of patients confirms results of previous studies 11, 23. In recent years, the diagnosis of SCA8 has been challenging owing to incomplete penetrance, and close attention to clinical setting and genetic criteria has been urged 10, 23–26. The patients in this study had repeat lengths that were in the range of other studies and the expansion segregated with the disease in the familial cases 11, 24.…”

Analysis of trinucleotide repeats in different SCA loci in spinocerebellar ataxia patients and in normal population of Taiwan

“…Recently, Cellini et al (2001) reported that the CTA/CTG repeats in the SCA8 locus varied from 15 to 75 triplets among normal individuals (29). The distribution of normal alleles in this study was similar to that previously reported in other ethnic groups (13,29). The most frequent allele contained 28 repeats, accounting for 16% of all normal controls analyzed.…”

CCG•CGG interruptions in high‐penetrance SCA8 families increase RAN translation and protein toxicity

“…Interestingly, four of the sporadic and two familial cases are homozygous and have two expanded alleles. These data and previous reports of expansion alleles in unaffected family members and in the general population (Moseley et al , 2000a; Stevanin et al , 2000; Worth et al , 2000; Cellini et al , 2001; Ikeda et al , 2004; Zeman et al , 2004) highlight the need to understand the molecular basis of the variable penetrance found in SCA8.…”