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Autosomal
Recessive Mental Retardation (ARMR)
The search
for
autosomal, i.e. non-X-linked genes that play a role in MR has been
largely
unsuccessful. At the onset of our
activities in this field
only three genes were known to
be associated
with non-syndromic ARMR: Neurotrypsin (Molinari
et al. 2002), which belongs to
the
subfamily of
trypsin-like serine
proteases, CRBN (cereblon) (Higgins
et al. 2004),
which
encodes an ATP-dependent Lon protease and CC2D1A a putative signal
transducer participating in positive regulation of I-κB kinase/NF-κB
cascade (Basel-Vanagaite
et al. 2005). This comparatively small number is due to the fact that
in western
civilizations
investigations of ARMR are hampered by insufficient
family sizes
and lack of consanguinity, which preclude successful mapping and
identification
of candidate loci. Together
with our collaboration Partners in Iran, we
are however able to overcome these unfavourable conditions by
investigating
highly consanguineous families from Iran, where the frequent occurrence
of
large families substantially facilitates autozygosity mapping and
subsequent
candidate
gene identification. In our project aiming at
the identification of new ARMR genes we are working on an still
growing cohort of more than 200 families and were so far able to
contribute 8 new genomic loci for non-syndromic forms of ARMR (Najmabadi
et al. 2007) and identify two novel genes for this disorder,
GRIK2 (Motazacker
et al. 2007) and TUSC3 (Garshasbi
et al. 2008), the latter being the first to show more than one
mutation in independent families from separate populations.
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Human Molecular
Genetics
