Analysis of SCA8 and SCA12 loci in 134 Italian ataxic patients negative for SCA1-3, 6 and 7 CAG expansions.
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.
Brusco
Alfredo
A
Unità Operativa Universitaria di Genetica Medica, Azienda Ospedaliera S. Giovanni Battista, via Santena 19, 10126, Torino, Italy. a.brusco@cios.to.cnr.it
Cagnoli
Claudia
C
Franco
Alessandra
A
Dragone
Elisa
E
Nardacchione
Antonella
A
Grosso
Enrico
E
Mortara
Paolo
P
Mutani
Roberto
R
Migone
Nicola
N
Orsi
Laura
L
D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D002648:Child; D018450:Disease Progression; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology; D018911:Trinucleotide Repeats
C415906:ATXN8OS gene product, human; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated