Myotonic dystrophy (DM) is the only disease reported tO be caused by a CTG expansion. We now report that a non-coding CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). This expansion, located on chromosome 13q21, was isolated directly from the genomic DNA of an ataxia patient by RAPID cloning. SCA8 patients have expansions similar in size (107-127 CTG repeats) to those found among adult-onset DM patients. SCA8 is the first example of a dominant SCA not caused by a CAG expansion translated as a polyglutamine tract.
Bibliographical noteFunding Information:
We thank family members for their participation, C. Peterson, H. Lipe and D. Nochlin for help developing the pedigrees and H. Orr for critically reading the manuscript. This work was supported by grants from the National Ataxia Foundation, the Bob Allison Ataxia Research Center, VA research funds and the National Institutes of Health (P01 NS33718 and RO1 NS36282).