Investigation of a family with DMD

Deletions occur in certain regions in 55% of
cases and duplications in 5%. However, point
mutations (in 40%) are not always detectable. In
this situation, indirect DNA analysis can be performed.
The panel shows a simplified example
of a two-allele system (marker DXS7). (Data
kindly provided by Dr. C. R. Müller-Reible, Institute
of Human Genetics, University of Würzburg).
Since the affected patients III-1 and III-2
carry the marker allele 1 at the DMD locus, allele
1 indicates the presence of the mutation.
The unaffected male II-4 confirms that allele 2
does not represent the mutation. The females
I-2, II-1, and II-2 are obligate heterozygotes
(2–1). In this example the males III-3 and III-4
are not affected. This can be explained by recombination
in their mother, II-5. In current
practice one uses a set of several linked markers
flanking the disease locus to avoid an erroneous
diagnosis due to recombination. Female heterozygotes
showmild clinical signs in 2–3%. About
23% of mothers of isolated patients are noncarriers.