例如:"lncRNA", "apoptosis", "WRKY"

Homozygous NLRP1 gain-of-function mutation in siblings with a syndromic form of recurrent respiratory papillomatosis.

Proc Natl Acad Sci U S A. 2019 Sep 17;116(38):19055-19063. Epub 2019 Sep 04
Scott B Drutman 1 , Filomeen Haerynck 2 , Franklin L Zhong 3 , David Hum 1 , Nicholas J Hernandez 1 , Serkan Belkaya 1 , Franck Rapaport 1 , Sarah Jill de Jong 1 , David Creytens 4 , Simon J Tavernier 5 , Katrien Bonte 6 , Sofie De Schepper 7 , Jutte van der Werff Ten Bosch 8 , Lazaro Lorenzo-Diaz 9 , Andy Wullaert 10 , Xavier Bossuyt 11 , Gérard Orth 12 , Vincent R Bonagura 13 , Vivien Béziat 9 , Laurent Abel 9 , Emmanuelle Jouanguy 9 , Bruno Reversade 14 , Jean-Laurent Casanova 15
Scott B Drutman 1 , Filomeen Haerynck 2 , Franklin L Zhong 3 , David Hum 1 , Nicholas J Hernandez 1 , Serkan Belkaya 1 , Franck Rapaport 1 , Sarah Jill de Jong 1 , David Creytens 4 , Simon J Tavernier 5 , Katrien Bonte 6 , Sofie De Schepper 7 , Jutte van der Werff Ten Bosch 8 , Lazaro Lorenzo-Diaz 9 , Andy Wullaert 10 , Xavier Bossuyt 11 , Gérard Orth 12 , Vincent R Bonagura 13 , Vivien Béziat 9 , Laurent Abel 9 , Emmanuelle Jouanguy 9 , Bruno Reversade 14 , Jean-Laurent Casanova 15
+ et al

[No authors listed]

Author information
  • 1 St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, 10065.
  • 2 Primary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, 9000 Ghent, Belgium.
  • 3 Lee Kong Chian School of Medicine, Nanyang Technological University, 636921 Singapore.
  • 4 Cancer Research Institute Ghent, Ghent University, 9000 Ghent, Belgium.
  • 5 Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
  • 6 Department of Otorhinolaryngology, Head and Neck Surgery, Craniofacial Team, Gent University Hospital, 9000 Ghent, Belgium.
  • 7 Department of Dermatology, Ghent University Hospital, 9000 Ghent, Belgium.
  • 8 Department of Pediatrics, Universitair Ziekenhuis Brussel, 1090 Jette, Belgium.
  • 9 Imagine Institute, Paris Descartes University, 75006 Paris, France.
  • 10 Center for Inflammation Research, Flanders Institute for Biotechnology, 9052 Ghent, Belgium.
  • 11 Department of Laboratory Medicine, University Hospitals Leuven, 3000 Leuven, Belgium.
  • 12 Department of Virology, Pasteur Institute, 75015 Paris, France.
  • 13 Division of Allergy and Immunology, Department of Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY 11549.
  • 14 Reproductive Biology Laboratory, Amsterdam UMC Netherlands, 1105 AZ Amsterdam, The Netherlands.
  • 15 HHMI, The Rockefeller University, New York, NY 10065.

摘要


Juvenile-onset recurrent respiratory papillomatosis (JRRP) is a rare and debilitating childhood disease that presents with recurrent growth of papillomas in the upper airway. Two common human papillomaviruses (HPVs), HPV-6 and -11, are implicated in most cases, but it is still not understood why only a small proportion of children develop JRRP following exposure to these common viruses. We report 2 siblings with a syndromic form of JRRP associated with mild dermatologic abnormalities. Whole-exome sequencing of the patients revealed a private homozygous mutation in NLRP1, encoding Nucleotide-Binding Domain Leucine-Rich Repeat Family Pyrin Domain-Containing 1. We find the NLRP1 mutant allele to be gain of function (GOF) for inflammasome activation, as demonstrated by the induction of inflammasome complex oligomerization and IL-1β secretion in an overexpression system. Moreover, patient-derived keratinocytes secrete elevated levels of IL-1β at baseline. Finally, both patients displayed elevated levels of inflammasome-induced cytokines in the serum. Six NLRP1 GOF mutations have previously been described to underlie 3 allelic Mendelian diseases with differing phenotypes and modes of inheritance. Our results demonstrate that an autosomal recessive, syndromic form of JRRP can be associated with an NLRP1 GOF mutation.

KEYWORDS: NLRP1, genetics, human papillomavirus, inflammasome, recurrent respiratory papillomatosis