Embed code
Note: this content has been automatically generated.
good morning everybody and thank you to
the organizing committee for accepting
my absolute casa our communication and
so susceptibility to your little Bistro
code is a real challenge in neonatal
infectious disease so in a population of
individuals exposed to the same
microorganism most cases on the small
proportion of infants will develop
life-threatening infection while the
majority of individuals would be
resistant to infection and this entering
the middle variability can be accounted
for by several known risk factors like
microbial risk factors micro below the
violence or host factors known facts is
no known to increase susceptibility to
infection like underlying medical
conditions the genetic factors but we're
infection occurs in otherwise healthy
infants without any known risk factors
and the operand risk factor for in
otherwise healthy newborns probably host
susceptibility place a major role so the
goal of our project is to resect the
molecular susceptibility of united group
b streptococcal disease to understand
which is the proportion of infants with
Group B Strep disease in which infection
can be explained by primary
immunodeficiency l also we have the
ambitious goal of possibly discovery
novel primary immunodeficiency that
account for isolated susceptibility to
group B strep disease so to this we need
of course approval from the community
and then we need to accurately select
patients patients with the most severe
phenotype permanent-like more likely to
be to have a monogenic condition
explaining the infectious phenotype we
need to prefer genomic studies through
next-generation sequencing technologies
and once mutations have been identified
we need to perform
of functional studies to correlate in a
prospective effect relationship
communication with the seller and
clinical phenotypes very simple to say
but actually very very difficult and
with several pitfalls so enrollment has
been ongoing over the past few years
thanks to the owner worldwide basis
actually and thanks to the efforts of
this we speak except studies with the
contribution of several needle units in
italy in Turkey in Australia Turkish
people have high incidence of
consanguinity this why we also included
that new units from Turkey and in blue
are depicted the counters were nu-metal
units are waiting approval from the
community for to join the network and so
far we have enrolled 97 patients and we
performed exome sequencing in 42 of them
and prioritization of patients was based
on some correct recent that made more
likely a monogenic condition to explain
the infectious phenotype so we
prioritized full-term babies over return
babies because return babies are more
likely to have an explanation for the
infection late-onset over early onset
infection because it's far from the
birth so it's probably less influenced
by maternal factors and of course
familia recursive or constant unity are
factors that increase the likelihood of
a melange any condition so we use under
matrix for exams sequencing and analysis
so in order to obtain through software
analysis to obtain a list of variance in
the cord the from to perform 30
downstream analysis and possibly
discover mutations variants that account
for the infectious phenotype so this is
the most difficult part because among
hundreds of thousands of variance we
have to to discover the only on the only
few variants that cause disease and
so who these needs of course filtering
and privatization according to several
criteria here and he said only son of
them so the rarity of the of the variant
in the general population and of course
we include only nonsynonymous variance
in the coding regions and we exclude in
the first analyses non-coding regions
because they're less likely to be
relevant to the disease and and we are
guided also buy some clinical
information like segregation families or
some additional information so this is
just an example of an ass on a subset of
the patients just to show you that
filtering allows to get rid of many of
the variants that are probably not
relevant to the disease but still we end
up with high numbers several hundreds
even thousands of variance the new
partner prioritisation so I was showing
the next few slides a few resources are
very preliminary Saturn nothing certain
for the moment because we found parents
mostly in single patients we increase
the co hurt but just to let you know
that after we got a sub set of variants
that have been obtained by filtering we
need additional protection by function
by pathway analysis and this is just an
example of two parents that seemed to
ask quite relevant to the disease
these are two genes that are involved in
not in the development of the immune
system so the the individual in the
mouse models are not developmental
defect immune system but but recent
affecting the response in the course of
infection and this variants are
interesting because they are destructive
of the program predicted to be disrupted
of the protein and that they're
heterozygous so consistent with a with a
sporadic occurrence of the disease in
the general population and this is just
to show you the variance in their
natural pathways so the signal
downstream from some cytokine receptors
and pattern recognition receptors and
induce white blood cell recruitment in
the course of infection cell growth and
differentiation and beasts of activation
infection so we are of course in the
very infancy of of of our project we
need for recruitment we need to
replicate this this result in additional
cases we need also to start thinking
about functional studies to validate
these findings and of course thinking
about other possible mechanisms to
explain infection where genetics does
not explain and this is just to thank
all the people that were involved so far

Share this talk: 


Conference program

Welcome Words
M. Roth-Kleiner, R. Arlettaz Mieth
10 jan. 2017 · 9:33 matin
Short Reports Introduction
E. Giannoni, T. Karen, Resp. Lausanne, Zürich
10 jan. 2017 · 9:38 matin
Association of Axonal Injury and Preeclampsia
Katrina Evers, Neonatology UKBB
10 jan. 2017 · 9:39 matin
Q&A - Association of Axonal Injury and Preeclampsia
Katrina Evers, Neonatology UKBB
10 jan. 2017 · 9:44 matin
Retinopathy of Prematurity
Roland Gerull, Bern
10 jan. 2017 · 9:47 matin
Q&A - Retinopathy of Prematurity
Roland Gerull, Bern
10 jan. 2017 · 9:54 matin
Parechovirus Infection: A Rare Cause of Neonatal Encephalitis (in French)
Dr Truant AS, Cheffe de clinique, Néonatologie, CHUV, Lausanne
10 jan. 2017 · 9:59 matin
Q&A - Parechovirus Infection: A Rare Cause of Neonatal Encephalitis
Dr Truant AS, Cheffe de clinique, Néonatologie, CHUV, Lausanne
10 jan. 2017 · 10:04 matin
Genetic Susceptibility to Neonatal Group B Streptococcal Disease
Alessandro Borghesi, Fellay lab, EPFL
10 jan. 2017 · 10:17 matin
Q&A - Genetic Susceptibility to Neonatal Group B Streptococcal Disease
Alessandro Borghesi, Fellay lab, EPFL
10 jan. 2017 · 10:25 matin
Psychomotor Development in Children Prenatally Exposed to Methadone
G. Grand-Guillaume-Perrenoud, Pediatrics, Children's University Hospital Geneva
10 jan. 2017 · 10:27 matin
Q&A - Psychomotor Development in Children Prenatally Exposed to Methadone
G. Grand-Guillaume-Perrenoud, Pediatrics, Children's University Hospital Geneva
10 jan. 2017 · 10:34 matin
Introduction to Christoph Berger's Presentation
C. Kind, R. Gerull, Resp. St.Gallen, Bern
10 jan. 2017 · 10:37 matin
Vertical Infections: An Update
Christoph Berger, Zürich
10 jan. 2017 · 10:40 matin
Q&A - Vertical Infections: An Update
Christoph Berger, Zürich
10 jan. 2017 · 11:15 matin
Introduction to Eric Giannoni's Presentation
R. Pfister, S. Kämpfen, Resp. Geneva, Basel
10 jan. 2017 · 11:44 matin
Sepsis, Antibiotics and Resistances: Where Are We?
Christoph Bührer, Berlin
10 jan. 2017 · 2:21 après-midi
Use and Abuse of Antibiotics in Neonatology
Martin Stocker, Lucerne
10 jan. 2017 · 2:50 après-midi
Panel Discussion : Controversies on Use of Antibiotics in Neonatology
Martin Stocker, Christoph Berger, Eric Giannoni, Christoph Bührer
10 jan. 2017 · 3:10 après-midi
Introduction to Christoph Bührer's Presentation
Romaine Arlettaz Mieth , Neonatologist, Zürich, President of the Organizing Committee
10 jan. 2017 · 3:47 après-midi
Evidence-Based Haemodynamic Management in Neonatal Sepsis
Christoph Bührer, Berlin
10 jan. 2017 · 3:48 après-midi
Q&A - Evidence-Based Haemodynamic Management in Neonatal Sepsis
Christoph Bührer, Berlin
10 jan. 2017 · 4:16 après-midi
SwissNeoDose Project
Marc Pfister, Ped Pharmacology, UKBB
10 jan. 2017 · 4:20 après-midi
Awards (Case of the Year; Milupa; Best Poster Case Report; Best Oral Short Presentation) & Closing Comments
Matthias Roth-Kleiner, CHUV, President of the SSN
10 jan. 2017 · 4:30 après-midi

Recommended talks

Rational protein design for vaccine development
Bruno Correia, Laboratory of Protein Design & Immunoengineering
16 mars 2017 · 11:39 matin