#604432
Table of Contents
A number sign (#) is used with this entry because of evidence that spinocerebellar ataxia-11 (SCA11) is caused by heterozygous mutation in the TTBK2 gene (611695), which encodes tau tubulin kinase-2, on chromosome 15q15.
Spinocerebellar ataxia-11 (SCA11) is a pure form of autosomal dominant cerebellar ataxia, which is a relatively benign, late-onset, slowly progressive neurologic disorder characterized by an uncomplicated cerebellar syndrome (Worth et al., 1999).
For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Worth et al. (1999) identified 2 British families with a relatively pure form of autosomal dominant cerebellar ataxia in which affected individuals did not have the CAG expansion in the CACNA1A gene (601011), excluding a diagnosis of SCA6 (183086), and in which the disease was not linked to the SCA5 (600224) or SCA10 (603516) loci.
Houlden et al. (2007) described an affected family from Devon, on the southwest coast of England, which stretched over 8 generations. Affected individuals had progressive cerebellar ataxia, abnormal eye signs and pyramidal features, as well as cerebellar atrophy visible upon magnetic resonance imaging.
Using a genomewide searching strategy in one of the British families described by them with autosomal dominant cerebellar ataxia, Worth et al. (1999) found linkage to marker D15S1039. Construction of haplotypes defined a 7.6-cM interval between the flanking markers D15S146 and D15S1016, thereby assigning the disease locus, designated SCA11, to chromosome 15q14-q21.3. They excluded linkage of the disease phenotype to this region in the second family.
Houlden et al. (2007) further localized the SCA11 locus to a 5.6-cM region containing 134 genes.
After screening 54 genes in a linkage region on chromosome 15q15-q21 in a large British family segregating SCA11, none of which had a pathogenic mutation, Houlden et al. (2007) analyzed the candidate gene TTBK2 (611695) and identified a heterozygous 1-base insertion (c.1329insA; 611695.0001). In a second family, of Pakistani origin, with SCA11, they identified a heterozygous 2-bp deletion (c.1284delGA; 611695.0002) in TTBK2.
Houlden, H., Johnson, J., Gardner-Thorpe, C., Lashley, T., Hernandez, D., Worth, P., Singleton, A. B., Hilton, D. A., Holton, J., Revesz, T., Davis, M. B., Giunti, P., Wood, N. W. Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nature Genet. 39: 1434-1436, 2007. Note: Erratum: Nature Genet. 40: 255 only, 2008. [PubMed: 18037885, related citations] [Full Text]
Worth, P. F., Giunti, P., Gardner-Thorpe, C., Dixon, P. H., Davis, M. B., Wood, N. W. Autosomal dominant cerebellar ataxia type III: linkage in a large British family to a 7.6-cM region on chromosome 15q14-21.3. Am. J. Hum. Genet. 65: 420-426, 1999. [PubMed: 10417284, related citations] [Full Text]
SNOMEDCT: 719207000; ORPHA: 98767; DO: 0050961;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 15q15.2 | Spinocerebellar ataxia 11 | 604432 | Autosomal dominant | 3 | TTBK2 | 611695 |
A number sign (#) is used with this entry because of evidence that spinocerebellar ataxia-11 (SCA11) is caused by heterozygous mutation in the TTBK2 gene (611695), which encodes tau tubulin kinase-2, on chromosome 15q15.
Spinocerebellar ataxia-11 (SCA11) is a pure form of autosomal dominant cerebellar ataxia, which is a relatively benign, late-onset, slowly progressive neurologic disorder characterized by an uncomplicated cerebellar syndrome (Worth et al., 1999).
For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Worth et al. (1999) identified 2 British families with a relatively pure form of autosomal dominant cerebellar ataxia in which affected individuals did not have the CAG expansion in the CACNA1A gene (601011), excluding a diagnosis of SCA6 (183086), and in which the disease was not linked to the SCA5 (600224) or SCA10 (603516) loci.
Houlden et al. (2007) described an affected family from Devon, on the southwest coast of England, which stretched over 8 generations. Affected individuals had progressive cerebellar ataxia, abnormal eye signs and pyramidal features, as well as cerebellar atrophy visible upon magnetic resonance imaging.
Using a genomewide searching strategy in one of the British families described by them with autosomal dominant cerebellar ataxia, Worth et al. (1999) found linkage to marker D15S1039. Construction of haplotypes defined a 7.6-cM interval between the flanking markers D15S146 and D15S1016, thereby assigning the disease locus, designated SCA11, to chromosome 15q14-q21.3. They excluded linkage of the disease phenotype to this region in the second family.
Houlden et al. (2007) further localized the SCA11 locus to a 5.6-cM region containing 134 genes.
After screening 54 genes in a linkage region on chromosome 15q15-q21 in a large British family segregating SCA11, none of which had a pathogenic mutation, Houlden et al. (2007) analyzed the candidate gene TTBK2 (611695) and identified a heterozygous 1-base insertion (c.1329insA; 611695.0001). In a second family, of Pakistani origin, with SCA11, they identified a heterozygous 2-bp deletion (c.1284delGA; 611695.0002) in TTBK2.
Houlden, H., Johnson, J., Gardner-Thorpe, C., Lashley, T., Hernandez, D., Worth, P., Singleton, A. B., Hilton, D. A., Holton, J., Revesz, T., Davis, M. B., Giunti, P., Wood, N. W. Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nature Genet. 39: 1434-1436, 2007. Note: Erratum: Nature Genet. 40: 255 only, 2008. [PubMed: 18037885] [Full Text: https://doi.org/10.1038/ng.2007.43]
Worth, P. F., Giunti, P., Gardner-Thorpe, C., Dixon, P. H., Davis, M. B., Wood, N. W. Autosomal dominant cerebellar ataxia type III: linkage in a large British family to a 7.6-cM region on chromosome 15q14-21.3. Am. J. Hum. Genet. 65: 420-426, 1999. [PubMed: 10417284] [Full Text: https://doi.org/10.1086/302495]
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