FM OCTOBER 2018 ISSUE - digital edition

employed genetic detection
test, which can detect up to
70% of DMD positive cases. EXON SKIPPING IS A
In the event of a negative MUTATION-SPECIFIC
MLPA result, clinicians THERAPY IN WHICH A
still have the option of
SMALL PIECE OF DNA CAN
confirming the disease using
BE INTRODUCED SUCH
next generation sequencing,
which can pick up about THAT IT WILL BIND TO A
98-99% of the positive PARTICULAR EXON.
cases. However, muscle
biopsy still remains the
final confirmatory test. In
this case, Dr. Shah proposed that MLPA be done, and the
results revealed that exon 43 was deleted, which confirmed
the clinical diagnosis of DMD. Genetic counselling would be
important in case the parents wish to have another child,
since prenatal genetic testing via MLPA at early stages of
pregnancy can help determine whether the male child
would have DMD. The prenatal tests can also help parents
decide whether they should terminate such a pregnancy.
Further, the parents of the boy were advised to get his sister
also genetically tested to determine if she was a carrier for
DMD mutation.
While currently there is no known cure for DMD, there is
hope for the future. Several research studies
have been carried out for different genetic
therapy approaches. Exon skipping is a
mutation-specific therapy in which a small
piece of DNA can be introduced such that it
will bind to a particular exon and encourage
the cell to skip reading that exon, thereby
effectively converting an out-of-frame
mutation to an in-frame mutation. Such
a therapy would allow DMD-type clinical
conditions to mimic BMD-type clinical
conditions, which are far more manageable
and have better prognosis. However, till
date, only a few specific therapies are
approved. For Dr. Shah’s patient, there is no
therapy for a deletion of exon 43. The only
US FDA approved therapy is for deletions
that can be corrected by skipping exon 51,
involved in about 13-20% of DMD cases.
However, research is ongoing, and it is likely
that other, newer exon-skipping targets
become available in the future.
DR SHIVANEE SHAH
OCTOBER 2018 / FUTURE MEDICINE / 59