Meiotic drive at the Myotonic Dystrophy locus

Carey, NJ, K.; Nokelainen, P.; Peltonen, L.; Savontaus, M. L.; Juvonen, V.; Anvret, M.; Grandell, U.; Chotai, K.; Robertson, E.; Middletonprice, H.; Malcolm, S.,  Nature Genetics,  6:117-118. 1994.

Myotonic dystrophy (DM) is the most common form of adult muscular dystrophy (average incidence 1 in 8,000) 1 • It is an autosomal dominant trait with multisystemic involvement and marked clinical variability. Anticipation, in which symptom severity increases and age of onset decreases in succeeding generations, is a common feature ofDM. The dynamic mutation underlying DM is the expansion of a CTG repeat in the 3′ untranslated region of a predicted cAMP-dependent protein kinase gene on chromosome 19q13.3 (refs 2-7). There is a broad correlation between repeat amplification and symptom severity in affected individuals; the normal unaffected repeat range is between 5 and 50 repeats: minimal symptoms are present in individuals with 50 to 80 repeats, but the repeat number becomes increasingly unstable on transmission when it exceeds 50. Severely affected patients may have CTG repeat expansions of several kilobases