SCA17
SCA17 is often associated with other problems such as dementia and epilepsy (Craig et al, 2005; Maltecca et al 2003; Rolfs et al 2003; Schneider et al, 2006).
The genetic cause of SCA17 has been identified as an expanded CAG/CAA repeat in the TBP gene (Nakamura et al, 2001). The TBP gene contains the code for a protein called the TATA-box binding protein, which is an important transcription factor (Kao et al 1990; Peterson et al 1990). Transcription factors control the transfer of genetic information from DNA, and TBP is believed to play a key role in the control of the activity of many genes as part of a large multi-protein complex called TFIID (White et al 1992).
The CAG/CAA repeats lead to clusters of the mutated TBP protein forming within the cell’s central body (nucleus). These are known as intranuclear inclusions and are commonly seen in the areas of the brain affected by SCA17 (Nakamura et al 2001; Rolfs et al, 2003).
The abnormal gene in SCA17 contains an increased number of CAG/CAA repeats. The higher the number of repeats, the earlier the symptoms begin to show. The abnormal gene may contain only CAG repeats or it may be a mixture of CAG and CAA (both sequences code for the amino acid glutamine). It is suggested that the presence of CAA interruptions stabilizes the repeat expansion as it is passed from generation to generation. This is thought to prevent the condition worsening in future generations, a process known as anticipation (Gao et al, 2008).
REFERENCES
Craig et al. J Neurol Sci, 2005; 239(1):105-108
Gao et al, 2008. J Hum Genet; 16(2): 215-222
Kao et al. Science, 1990; 248(4963): 1645-1650
Maltecca et al. Neurology, 2003; 61: 1441-1443
Nakamura et al. Hum Mol Genet, 2001; 10(14):1441-1448
Peterson et al. Science, 1990; 248(4963): 1625-1630
Rolfs et al. Ann Neurol 2003; 54(3): 367-375
Schneider at al. Neurology, 2006; 67(9): 1701-1703
White et al. J Cell Sci Suppl, 1992: 16:1-7
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