425Genetic Testing for HD
Predictive testing for HD had been available for some time before the HD gene was
cloned. In these procedures, polymorphic markers, fl anking the HD gene and located
some distance from it, were used to track the disease allele through affected pedi-
grees. This indirect method yielded probabilistic results. Direct mutation analysis of
the HD gene is now possible and gives more accurate results. Measurement of the
number of cytosine, adenine, and guanine (CAG) repeats in the HD gene represents
an effective, direct test with which to confi rm the clinical diagnosis in diffi cult cases.
Genetic testing for HD is a success story so far and should serve as a model for
presymptomatic testing of other adult-onset presymptomatic disorders, but there are
some errors. The region around and within the CAG repeat sequence in the HD gene
is a hot spot for DNA polymorphisms, which can occur in up to 1 % of subjects
tested for HD. These polymorphisms may interfere with amplifi cation by PCR, and
so have the potential to produce a diagnostic error. Further refi nements in diagnos-
tics are desirable.
Personalized Cell Therapy for Huntington Disease
Human iPSCs derived from Huntington disease (HD) patient fi broblasts can be cor-
rected by the replacement of the expanded CAG repeat with a normal repeat using
homologous recombination, and that the correction persists in iPSC differentiation
into DARPP-32-positive neurons in vitro and in vivo (An et al. 2012 ). Further, cor-
rection of the HD-iPSCs normalized pathogenic HD signaling pathways (cadherin,
TGF-β, BDNF, and caspase activation) and reversed disease phenotypes such as
susceptibility to cell death and altered mitochondrial bioenergetics in NSCs. The
ability to make patient-specifi c, genetically corrected iPSCs from HD patients will
provide relevant disease models in identical genetic backgrounds and is a critical
step for the eventual use of these cells in cell replacement therapy.
Personalized Management of Epilepsy
Epilepsy is mostly a multifactorial disorder although familial forms occur and some
epilepsy genes have been identifi ed. With no known intervention to prevent or cure
epilepsy, treatment is primarily symptomatic and requires long-term administration
of medications to suppress seizure occurrence. Currently, a trial-and-error approach
is employed to choose the most effective antiepileptic drug (AED) for a patient
from numerous choices, but ~30 % of all patients are resistant to AED therapy,
which can be partially attributed to the presence of polymorphisms of genes encod-
ing enzymes involved in AED metabolism.
Personalized Management of Epilepsy