536
Gene expression profi ling of hind limb muscles of mouse models of muscular
dystrophies can clearly discriminate between severely affected and mildly or nonaf-
fected animals. Dystrophin-defi cient and sarcoglycan-defi cient profi les are remark-
ably similar, sharing infl ammatory and structural remodeling processes. These
processes were also ongoing in dysferlin-defi cient animals, although at lower lev-
els, in agreement with the later age of onset of this muscular dystrophy. The infl am-
matory proteins Spp1 and S100a9 were up-regulated in all models. This study has
identifi ed biomarker genes for which expression correlates with the severity of the
disease. This comparative study is an important step toward the development of an
expression profi ling-based diagnostic approach for muscular dystrophies in humans.
Biomarkers of Phenylketonuria
Phenylketonuria (PKU) is a genetic disease affecting 1:10,000–14,000 live births.
In this condition, phenylalanine hydroxylase (PAH) defi ciency is inherited as an
autosomal recessive trait and the associated hyperphenylalaninemia phenotype is
highly variable. Neurological abnormalities in phenylketonuria include tremor,
clumsiness, epilepsy, spastic paraparesis and intellectual impairment. Screening for
PKU was introduced in the UK >30 years ago and has proved successful in prevent-
ing severe mental retardation. Genotype-based prediction of the biochemical phe-
notype is now feasible in the majority of newborns with hyperphenylalaninemia,
which may be useful for refi ning diagnosis and anticipating dietary requirements.
Methods currently used to screen for PKU include spectrophotometry, fl uorometry,
immunoassay, and tandem mass spectrometry with electrospray ionization.
Developments in tandem mass spectrometry have made it technically possible to
screen for several inborn errors of metabolism in a single analytical step. NeoLynx
Screening Application-Manager (Waters Corporation) is indicated for the quantita-
tive measurement of phenylalanine and tyrosine in neonatal blood samples by tan-
dem mass spectrometry – exclusively with Quattro micro/Quattro LC mass
spectrometers. Additionally, measurements of tyrosine can be used as an adjunct to
the measurement of phenylalanine in reducing the number of false-positive results
with NeoLynx Screening Application-Manager.
Genetic Biomarkers for Psoriasis
Psoriasis is a common, immune-mediated genetic disorder of the skin and is associ-
ated with arthritis in ~30 % of cases. PSORS2 (psoriasis susceptibility locus 2) has
been localized to chromosomal region 17q25.3-qter after a genome-wide linkage
scan in a family of European ancestry with multiple cases of psoriasis and psoriatic
arthritis. In caspase recruitment domain family, member 14 (CARD14), the same
authors identifi ed unique gain-of-function mutations that segregated with psoriasis
16 Personalized Management of Genetic Disorders