455patient centered personalized care. The fi nding that higher REM density in depressed
patients is associated with better response including sleep to Corticotropin-releasing
hormone receptor-1 antagonists indicates the importance of using such biomarkers
to fi nd the right sleeping drug for the right patient.
Personalized Approach to Chronic Fatigue Syndrome
Chronic fatigue syndrome (CFS) is a complex illness that includes alterations in
multiple body systems and results from the combined action of many genes and
environmental factors. Genomic studies including SNPs have linked CFS to fi ve
mutations in three genes coding for the glucocorticoid receptor, for serotonin, and
for tryptophan hydroxylase that are related to the body’s ability to handle stress
(Vernon and Reeves 2006 ). The fi ndings provide evidence of the biological basis of
CFS and could lead to improved diagnostic tools and new therapies. Using an inte-
grated genomic approach, a study suggests the possible role for genes involved in
glutamatergic neurotransmission and circadian rhythm in CFS and supports further
study of novel candidate genes in independent populations of CFS subjects (Smith
et al. 2011 ). Another study used functional and structural equation modeling
approaches to assess the contributions of the polymorphism (rs6311), DNA meth-
ylation and clinical variables to HTR2A expression in CFS subjects from a
population- based study (Falkenberg et al. 2011 ). Results suggests that rs6311 can
affect both transcription factor binding and promoter methylation, and this along
with an individual’s stress response can impact the rate of HTR2A transcription in
a genotype and methylation-dependent manner.
Personalized Approach to Ataxias
A pilot study has used heterogeneous ataxias as a model neurogenetic disorder to
assess the introduction of NGS into clinical practice (Németh et al. 2013 ). The
authors captured several known human ataxia genes by use of NGS in patients with
ataxia who had been extensively investigated and were refractory to diagnosis.
Pathogenicity was assessed using a bioinformatics approach and novel variants
were validated using functional experiments. The overall detection rate in this study
was 18 % and varied from 8.3 % in those with an adult onset progressive disorder
to 40 % in those with a childhood or adolescent onset progressive disorder. The
majority of cases with detectable mutations had a childhood onset but most are now
adults, refl ecting the long delay in diagnosis. The delays were primarily related to
lack of easily available clinical testing, but other factors included the presence of
atypical phenotypes and the use of indirect testing. Sequencing was highly effi cient
and the consumable cost was ∼$620. The pathogenicity interpretation pathway pre-
dicted numerous mutations in eight different genes: PRKCG, TTBK2, SETX,
Personalized Approach to Ataxias