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

Abstract

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.

Spinocerebellar ataxia type 12

“…The SCA12 mutation was not detected in a patient population that included 180 North American ataxia kindreds of European, Chinese, Japanese, Southeast Asian, East Indian, Middle Eastern, Hispanic, or African-American ethnic descent (Cholfin et al, 2001). The SCA12 mutation has not been found among patients with ataxia of unknown cause in other countries, including the United Kingdom (Worth and Wood, 2001), Italy (Brusco et al, 2002), Portugal or Brazil (Silveira et al, 2002), the Netherlands (van de Warrenburg et al, 2002), Japan (Maruyama et al, 2002;Matsumura et al, 2003), Taiwan, East India (Sinha et al, 2004), Poland (Sułek et al, 2004), or Serbia (Dragasević et al, 2006).…”

Cognitive impairment in spinocerebellar ataxia type 8

“…However, they did not report either the neuropsychological methods or the criteria for cognitive impairment used in their studies. In three other studies [6,8,19], cognitive functioning has been evaluated using the MMSE, which has been reported to be an insensitive measure of cognitive performances [20]. Zeman et al used, besides MMSE, also the AddenbrookeVs Cognitive Examination, which is, with their own words, insensitive to subtle neuropsychological deficits and executive dysfunction, and neither of the tests did reveal cognitive deterioration.…”

Non-Ataxic Phenotypes of SCA8 Mimicking Amyotrophic Lateral Sclerosis and Parkinson Disease

“…A large number of clinical analyses have demonstrated that SCA8 presents as a very slowly progressive ataxia,13,14 and affected individuals displayed gait, limb ataxia, speech, and oculomotor incoordination. However, there have been several reports of nonataxic symptoms of SCA8 as atypical phenotypes in the past decade.…”