Maternal anticipation in Machado-Joseph disease (MJD): some maternal factors independent of the number of CAG repeat units may play a role in genetic anticipation in a Japanese MJD family

We studied the relationship between the number of CAG repeat units in the MJD1 gene and clinical features of Machado-Joseph disease (MJD) in eight patients from two generations of a Japanese MJD family. Because of lack of characteristic clinical signs of MJD such as dystonia, bulging eyes or facial myokymia, clinical diagnosis of MJD in this family was difficult to make prior to molecular testing for the CAG repeat expansion in the MJD1 gene. All the patients exhibited maternal transmission of MJD, and the intergenerational change in the number of CAG repeat units in the MJD1 gene was very small (+0.5±0.3, mean±S.E.M., n=4) in spite of marked genetic anticipation (−17.0 years/generation). In the present family, the degree of anticipation per repeat unit in maternal transmissions was much larger than that in maternal transmissions in the other six MJD families. This indicates that some maternal factors other than the increase of the number of CAG repeat units, which is known to be the basis of anticipation, may play a role in genetic anticipation in this MJD family.