Molecular Genetics of Neuromuscular Disease 
might yield a mild memal impairment, explain- 
ing the mental phenotype observed in Duchenne 
patients. 
Abnormalities of dystrophin are easily detected 
at the protein level, and nearly 70 percent of mu- 
tations that cause these abnormalities have been 
shown to be deletions or duplications of some 
part of this extremely large locus. The remaining 
mutations are probably single-base changes that 
either disrupt translation of a functional protein 
or affect the processing of the large primary dys- 
trophin transcript. 
We have designed primers from dystrophin's 
nucleotide sequence to allow polymerase chain 
reaction (PGR) amplification of specific regions 
of the protein's transcript. By looking at the tran- 
script, we should be able to determine the nature 
of these other mutations and to follow them in 
families at risk of having inherited such muta- 
tions. This ability will improve the diagnosis of 
Duchenne dystrophy and complement existing 
methods. 
Our aim for the future year is to build on work 
already in progress. We will continue to identify, 
clone, and study new dystrophin relatives with an 
eye toward their possible role in mitigating the 
effects of abnormal dystrophin. We will also 
study any possible role these proteins might play 
in other neuromuscular diseases. As more disease 
loci are mapped to regions of human chromo- 
somes, our candidate gene approach should help 
in the rapid characterization of these diseases. 
252 
