We report the mapping of a second myotonic dystrophy locus, myotonic d
ystrophy type 2 (DM2). Myotonic dystrophy (DM) is a multi-system disea
se and the most common form of muscular dystrophy in adults'. In 1992,
DM was shown to be caused by an expanded CTG repeat in the 3' untrans
lated region of the dystrophia myotonica-protein kinase gene (DMPK) on
chromosome 19 (refs 2-6). Although several theories have been put for
th to explain how the CTC expansion causes the broad spectrum of clini
cal features associated with DM, it is not understood how this mutatio
n, which does not alter the protein-coding region of a gene, causes an
affect at the cellular level(7,8). We have identified a five-generati
on family (MN1) with a generically distinct form of myotonic dystrophy
. Affected members exhibit remarkable clinical similarity to DM (myoto
nia, proximal and distal limb weakness, frontal balding, cataracts and
cardiac arrhythmias) but do not have the chromosome-19 CTG expansion.
We have mapped the disease locus (DM2) of the MN1 family to a 10-cM r
egion of chromosome 3q. Understanding the common molecular features of
two different forms of the disease should shed right on the mechanism
s responsible for the broad constellation of seemingly unrelated clini
cal features present in both diseases.