Zoghbi, Huda
<p>Apr 13, 2014 03:36 PM</p>
<p>
ZOGHBI, Huda, MeCP2 and Neuropsychiatry, Baylor, April 10, 2014
Lecture at Stanford in Berg Hall in LKS Center at noon.
this is the Eric Shooter lecture (founder of our neurosci dept)</p>
<p>
intro by Prof. Ben Barras (Chair of Neurosci at Stfd)</p>
<p>
her title is A Neural Tipping Point: MeCP2 and Neuropsychiatric Disorders</p>
<p>
Huda is an HHMI investig; she is at Baylor College of Med and Texas Children's Hosp..</p>
<p>
Eric Shooter: first to isolate NGF nerve growth factor; did neurotrophin research;</p>
<p>
her bach. from American Univ in Beirut;</p>
<p>
MD and PhD: has focused on Rett's Syndrome;</p>
<p>
2000 Instit of Med and NAS member; many top prizes: </p>
<p>
she starts **</p>
<p>
she studied pedi neurology...</p>
<p>
1983 at Texas Chidlren's Hospital Rett's Syndrome</p>
<p>
shows video clip of a toddler with Rett's: cannot use hands;
she wrings her hands and has an abnl gait;
was born normal but gradually worsens...</p>
<p>
1983 Ann Neuro A progressive Syndrome of Autism,
Dementia, Ataxia and Loss of Puposeful Hand Use in Girls: Rett's Syndrome
by Hagberb...
she saw that report and thought that's what her pt had.</p>
<p>
next saw another adult with Rett's: video clip;</p>
<p>
she then did chart review and then had largest series of pts.</p>
<p>
in 1985 she pub NEJM article:</p>
<p>
reduction of biogenic amine levels in the Rett Syndrome</p>
<p>
had 200 pts... time to go to the lab to study this...</p>
<p>
challenge to gene ID: Rett synd is sporadic...</p>
<p>
but rare familial cases provide a clue</p>
<p>
must be on the X chromosome...</p>
<p>
only one X active in every cell...</p>
<p>
but X chromosome inactivation in one or two asymptomatic carriers.</p>
<p>
then another family: half-cousins with Rett Syndrome</p>
<p>
her hunch... this must be a genetic disorder..</p>
<p>
but then 1995: study claimed that Rett was NOT a genetic disorder.</p>
<p>
but then another study... got it down to 10 megabase region on X chromo...</p>
<p>
Methyl Cytosine binding protein = MECP2.</p>
<p>
Loss of MeCP2 function in females can causes any of the followingt:</p>
<p>
typical Rett
atpic Rett
mild cog deficit
cog defic with seizures
cog def, anxiety and OCD
Autism...</p>
<p>
shows video clips: spectrum of phenotypes
autism, bad dystonias, etc.</p>
<p>
oss of MeCP2 function in males</p>
<p>
neonatal enceph and eath within 1st year of lifeAutism, etc.</p>
<p>
We (and others) created mouse model for Rett...</p>
<p>
she vidoe clips: normal mouse and
Rett mouse (wringing its paws!!!)</p>
<p>
gene causes loss of function...</p>
<p>
also did a model in which they doubled level of protein (MECP2)</p>
<p>
MECP2 is pronounced MEC P two.</p>
<p>
she looked for and found male swith duplciated MECP2... video clip of 7 year old boy;</p>
<p>
boy comes from a 3 generation family with MECP2 duplication... per Ramocki in Annals of Neuro.</p>
<p>
summary: must have this protein at just the right amount:</p>
<p>
get syndromes if too much or too little; v dosage sensitive;</p>
<p>
she shows graph: need to have 100% of Mecp2 level if doubled: sever syndrome</p>
<p>
and if zero, sever syndrome with everything in btwn.</p>
<p>
Chao in Neuron in 2007;</p>
<p>
MeCP2 modulates the # of glutamaergic synapses.</p>
<p>
shows fluor of synapses:
2X mecp2: huge # of synapses
versus mecp2 null: get syanpses but they are sparse compared to sild type mouse.</p>
<p>
so, we needed to look at synapse regulation in relation to MECP2</p>
<p>
(note: schedule conflict: I bike to SRI for Robo Madness qv) time is 12:30PM.
I was not able to hear end of this brilliant talk.)
L
</p>