SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein

Abstract

Genetic etiologies of at least 20% of autosomal dominant cerebellar ataxias (ADCAs) have yet to be clarified. We identified a novel spinocerebellar ataxia (SCA) form in four Japanese pedigrees which is caused by an abnormal CAG expansion in the TATA-binding protein (TBP) gene, a general transcription initiation factor. Consequently, it has been added to the group of polyglutamine diseases. This abnormal expansion of glutamine tracts in TBP bears 47--55 repeats, whereas the normal repeat number ranges from 29 to 42. Immunocytochemical examination of a postmortem brain which carried 48 CAG repeats detected neuronal intranuclear inclusion bodies that stained with anti-ubiquitin antibody, anti-TBP antibody and with the 1C2 antibody that recognizes specifically expanded pathological polyglutamine tracts. We therefore propose that this new disease be called SCA17 (TBP disease).

Spectrum and prevalence of autosomal dominant spinocerebellar ataxia in Hokkaido, the northern island of Japan: a study of 113 Japanese families

“…Expanded triplet repeats in the genes causing SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, and DRPLA were amplified using the primer pairs Rep-1/ Rep-2 (Orr et al 1993), F-1/F-2 (Sanpei et al 1996), MJD25/ MJD52 (Kawaguchi et al 1994), S-5-F1/ S-5-R1 (Zhunchenko et al 1997), 4U1024/4U716 (David et al 1997), SCA8-F3/SCA8-R4 (Koob et al 1999), PPP2R2B-A/PPP2R2B-B (Holmes et al 1999), TBP-F/TBP-R (Nakamura et al 2001) and CTG-B37(699)/(840) (Koide et al 1994) respectively. We did not test for the SCA10 mutation, because its clinical manifestation is ataxia with seizure, which was not observed in our ADCA families.…”

“…To date, 29 different genetic loci have been reported to be responsible for ADCA (http://www.gene.ucl.ac.uk/cgi-bin/nomenclature): spinocerebellar ataxia type 1 (SCA1) on chromosome 6p22-p23 (Orr et al 1993); SCA2 on 12q23-q24.1 (Imbert et al 1996;Sanpei et al 1996); Machado-Joseph disease (MJD)/ SCA3 on 14q24.3-q32.1 (Kawaguchi et al 1994); SCA4 on 16q22.1 (Flanigan et al 1996); SCA5 on 11q13.2 (Ranum et al 1994); SCA6 on 19p13.1 (Zhuchenko et al 1997); SCA7 on 3p12-p13 (David et al 1997); SCA8 on 13p (Koob et al 1999); SCA10 on 22q13-qter. (Matsuura et al 2000); SCA11 on 15q14-q21.3 (Worth et al 1999); SCA12 on 5q31-33 (Holmes et al 1999);SCA13 on 19q13.3-q13.4 (Waters et al 2006); SCA14 on 19q13.42 Chen et al 2003;Yabe et al 2003); SCA15 on 3p24.2 (Gardner et al 2005); SCA16 on 8q23-q24.1 (Miyoshi et al 2001); SCA17 on 6q27 (Nakamura et al 2001); SCA18 on 7q22 (Brkanac et al 2002); SCA19 on 1p21-q21 (Verbeek et al 2002); SCA20 on 11p11.2-q13.3 (Knight et al 2004); SCA21 on 7p21.3-p15.1 (Vuillaume et al 2002); SCA22 on 1p21-q23 (Chung et al 2003); SCA23 on 20p13-p12 (Verbeek et al 2004); SCA24 on 1p26 (Swartz et al 2002); SCA25 on 2p21-p15 (Stevanin et al 2004); SCA26 on 19p13.3 (Yu et al 2005); SCA27 on 13q33.1 (Van Swieten et al 2003); SCA28 on 18p11.22-q11.2 (Cagnoli et al 2006); SCA 29 on 3p26 (Dudding et al 2004) and dentatorubral pallidoluysian atrophy (DRPLA) on 12p13.31 (Koide et al 1994;Nagafuchi et al 1994). Among these loci, causative genes have been further identified containing trinucleotide repeats (CAG) in S...…”

“…(Matsuura et al 2000); SCA11 on 15q14-q21.3 (Worth et al 1999); SCA12 on 5q31-33 (Holmes et al 1999);SCA13 on 19q13.3-q13.4 (Waters et al 2006); SCA14 on 19q13.42 Chen et al 2003;Yabe et al 2003); SCA15 on 3p24.2 (Gardner et al 2005); SCA16 on 8q23-q24.1 (Miyoshi et al 2001); SCA17 on 6q27 (Nakamura et al 2001); SCA18 on 7q22 (Brkanac et al 2002); SCA19 on 1p21-q21 (Verbeek et al 2002); SCA20 on 11p11.2-q13.3 (Knight et al 2004); SCA21 on 7p21.3-p15.1 (Vuillaume et al 2002); SCA22 on 1p21-q23 (Chung et al 2003); SCA23 on 20p13-p12 (Verbeek et al 2004); SCA24 on 1p26 (Swartz et al 2002); SCA25 on 2p21-p15 (Stevanin et al 2004); SCA26 on 19p13.3 (Yu et al 2005); SCA27 on 13q33.1 (Van Swieten et al 2003); SCA28 on 18p11.22-q11.2 (Cagnoli et al 2006); SCA 29 on 3p26 (Dudding et al 2004) and dentatorubral pallidoluysian atrophy (DRPLA) on 12p13.31 (Koide et al 1994;Nagafuchi et al 1994). Among these loci, causative genes have been further identified containing trinucleotide repeats (CAG) in SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, DRPLA (Orr et al 1993;Sanpei et al 1996;Kawaguchi Y et al 1994;Zhuchenko et al 1997;David et al 1997;Nakamura et al 2001;Koide et al 1994), and in the promoter region of PPP2R2B related to SCA12 (Holmes et al 1999); trinucleotide repeats (CTG) within an untranslated region of the SCA8 gene (Koob et al 1999); and a pentanucleotide (ATTCT) repeat expansion within intron 9 of the SCA10 gene (Matsuura et al 2000). Whi...…”

Exclusion of mutations in the PRNP, JPH3, TBP, ATN1, CREBBP, POU3F2 and FTL genes as a cause of disease in Portuguese patients with a Huntington-like phenotype

“…This is the case for some forms of autosomal dominant cerebellar ataxia, specifically spinocerebellar ataxia type 17 (SCA17) (Koide et al 1999;Nakamura et al 2001), and dentatorubropallidoluysian atrophy (DRPLA) (Koide et al 1994), which may show clinical features similar to those of HD, namely dementia, chorea, Parkinsonism and dystonia. SCA17 is caused by an expansion of a CAA/ CAG repeat segment on the TATA-binding protein gene (TBP), and DRPLA is also caused by an expansion of a (CAG) n in the gene encoding athrophin-1 (ATN1).…”

C‐terminal deletion of the atrophin‐1 protein results in growth retardation but not neurodegeneration in mice

“…Unstable expansion of poly-Q has been identified as a common mutation in several neurodegenerative disorders such as Huntington's disease (HD), spinobulbar muscular atrophy (SBMA), and at least six types of spinocerebellar ataxia (SCA1, 2, 3, 6, 7, and 17) (Ross, 1995;Ross et al, 1998;Nakamura et al, 2001). Disease genes share no sequence homology except for the poly-Q coding sequences, indicating a critical role of the glutamine expansion in pathogenesis (Igarashi et al, 1998).…”