dementia-2018-scientifictracks

6 / 7

Page 23
Notes:
allied
academies
August 16-17, 2018 | Copenhagen, Denmark
Dementia and Alzheimer ’s Disease
10th World congress on
Journal of Neurology and Neurorehabilitation Research | Volume: 3
Loss-of-function mutation in RUSC2 causes ntellectual disability and secondary microcephaly
Ali H Alwadei
King Fahad Medical City, Riyadh, Saudi Arabia
Intellectual disability is seen in up to 1% to 3% of the general
population, and isoftendichotomized intosyndromicandnon-
syndromic forms. A genetic aetiology accounts for about 25% to
50% of cases, with up to 700 monogenic mutations identified
so far. Recent advances in genetic testing have allowed the
identification of an ever-increasing repertoire of genes causing
intellectual disability. Characterization of their protein products
has shed light onto the diverse biological pathways affected in
this important neurological disease that results in significant
impairment in cognitive and adaptive behaviour, and which
has important medical and social implications. Aberrancies in
synaptic vesicular transport and intracellular protein trafficking
have been highlighted among the various biological pathways
reported to cause intellectual disability. Included in these
are mutations in genes coding for Rab proteins (rabaptins),
a group of small Ras GTPases that have been shown to play
an important role at different levels of the cellular trafficking
pathway. Although over 60 Rab proteins have been identified
so far, only a few have been implicated in human disease,
including in patients with intellectual disability with or without
associated brain malformations. RUSC2, officially known as
RUN and SH3 domain containing a gene found on chromosome
9p13.3 (gene identifier [ID] 9853, Mendelian Inheritance in
Man [MIM] 611053). RUSC2 codes for iporin, a ubiquitous
protein with moderate to high expression in the human brain.
The literature on the functions of iporin remains sparse, but
there is some evidence that it interacts with Rab1b and Rab1-
binding protein GM130,10 both of which are also expressed
in the brain, with highest expression in dendritic spines where
they appear to play an important role in synaptogenesis. So
far, no mutations in RUSC2 have ever been shown to cause
human disease, and no animal models disrupting this gene
have been described. However, to our knowledge for the
first time, we describe the clinical presentations of three
patients (two male siblings and one unrelated female) with
severe intellectual disability and microcephaly. Through
whole-exome sequencing, all three were found to have
inherited homozygous nonsense mutations in RUSC2.
Speaker Biography
Ali H Alwadei currently works at Pediatric Neurology Department, National
Neuroscience Institute, King Fahad Medical City, Saudi Arabia.
e: