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

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Conference program

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