Imperial College London
Professor Michael Way

ProfessorMichaelWay

Faculty of Medicine, Department of Infectious Disease

Professor of Virology
 
 
 
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Contact

 

+44 (0)20 3796 2068michael.way1 Website

 
 
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Location

 

Francis Crick InstituteThe Francis Crick Institute

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Summary

 

Publications

Citation

BibTex format

@article{Sindram:2023:10.1101/2023.01.19.524688,
author = {Sindram, E and Caballero-Oteyza, A and Kogata, N and Huang, S and Alizadeh, Z and Gamez-Diaz, L and Fazlollhi, MR and Peng, X and Grimbacher, B and Way, M and Proietti, M},
doi = {10.1101/2023.01.19.524688},
title = {ARPC5 deficiency leads to severe early onset systemic inflammation and early mortality},
url = {http://dx.doi.org/10.1101/2023.01.19.524688},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>The seven subunit Arp2/3 complex drives the formation of branched actin networks that are essential for many cellular processes including cell migration. In humans, the ARPC5 subunit of the Arp2/3 complex is encoded by two paralogous genes (<jats:italic>ARPC5</jats:italic>and<jats:italic>ARPC5L</jats:italic>), resulting in proteins with 67% identity. Through whole-exome sequencing, we identified a biallelic ARPC5 frameshift variant in a female child who presented with recurrent infections, multiple congenital anomalies, diarrhea, and thrombocytopenia, and suffered early demise from sepsis. Her consanguineous parents also had a previous child who died with similar clinical features. Using CRISPR/Cas9-mediated approaches, we demonstrate that loss of ARPC5 affects actin cytoskeleton organization and function, as well as chemokine-dependent cell migration<jats:italic>in vitro</jats:italic>. Homozygous<jats:italic>Arpc5</jats:italic>-/- mice do not survive past embryonic day 9 due to severe developmental defects, including loss of the second pharyngeal arch which contributes to craniofacial and heart development. Our results indicate that ARPC5 is important for both prenatal development and postnatal immune signaling, in a non-redundant manner with ARPC5L. Moreover, our observations add the<jats:italic>ARPC5</jats:italic>locus to the list of genes that should be considered when patients present with syndromic early-onset immunodeficiency, particularly if recessive inheritance is suspected.</jats:p>
AU  - Sindram,E
AU  - Caballero-Oteyza,A
AU  - Kogata,N
AU  - Huang,S
AU  - Alizadeh,Z
AU  - Gamez-Diaz,L
AU  - Fazlollhi,MR
AU  - Peng,X
AU  - Grimbacher,B
AU  - Way,M
AU  - Proietti,M
DO  - 10.1101/2023.01.19.524688
PY  - 2023///
TI  - ARPC5 deficiency leads to severe early onset systemic inflammation and early mortality
UR  - http://dx.doi.org/10.1101/2023.01.19.524688
ER  -
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