TY - JOUR T1 - Factors associated with <em>HD</em> CAG repeat instability in Huntington disease JF - Journal of Medical Genetics JO - J Med Genet SP - 695 LP - 701 DO - 10.1136/jmg.2007.050930 VL - 44 IS - 11 AU - V C Wheeler AU - F Persichetti AU - S M McNeil AU - J S Mysore AU - S S Mysore AU - M E MacDonald AU - R H Myers AU - J F Gusella AU - N S Wexler AU - The US–Venezuela Collaborative Research Group Y1 - 2007/11/01 UR - http://jmg.bmj.com/content/44/11/695.abstract N2 - Background: The Huntington disease (HD) CAG repeat exhibits dramatic instability when transmitted to subsequent generations. The instability of the HD disease allele in male intergenerational transmissions is reflected in the variability of the CAG repeat in DNA from the sperm of male carriers of the HD gene.Results: In this study, we used a collection of 112 sperm DNAs from male HD gene-positive members of a large Venezuelan cohort to investigate the factors associated with repeat instability. We confirm previous observations that CAG repeat length is the strongest predictor of repeat-length variability in sperm, but we did not find any correlation between CAG repeat instability and either age at the time of sperm donation or affectedness status. We also investigated transmission instability for 184 father–offspring and 311 mother–offspring pairs in this Venezuelan pedigree. Repeat-length changes were dependent upon the sex of the transmitting parent and parental CAG repeat length but not parental age or birth order. Unexpectedly, in maternal transmissions, repeat-length changes were also dependent upon the sex of the offspring, with a tendency for expansion in male offspring and contraction in female offspring.Conclusion: Significant sibling–sibling correlation for repeat instability suggests that genetic factors play a role in intergenerational CAG repeat instability. ER -