CAG-SIZE SPECIFIC RISK ESTIMATES FOR INTERMEDIATE ALLELE REPEAT INSTABILITY IN HUNTINGTON DISEASE

New mutations for Huntington disease occur due to CAG repeat expansion of intermediate alleles. While intermediate alleles (27-35 CAG) usually do not confer the disease phenotype, they are prone to paternal germline CAG repeat instability. Consequently, they may expand into the HD range upon transmission to the next generation producing a new mutation. We report the frequency and magnitude of CAG repeat instability, including repeat contraction and expansion, across the entire range of intermediate CAG sizes. Our findings demonstrate a significant risk of new mutations, particularity for intermediate alleles with 34 & 35 CAG repeats. These quantified CAG-size specific risk estimates inform clinical practice and provide accurate information for persons with an intermediate allele. (By Dr. Alicia Semaka, http://jmg.bmj.com/content/early/2013/07/29/jmedgenet-2013-101796 )