228 230

Cited 238 times in

Mutations in NALP12 cause hereditary periodic fever syndromes

Authors
 I. Jéru  ;  P. Duquesnoy  ;  T. Fernandes-Alnemri  ;  E. Cochet  ;  J. W. Yu  ;  M. Lackmy-Port-Lis  ;  E. Grimprel  ;  J. Landman-Parker  ;  V. Hentgen  ;  S. Marlin  ;  K. McElreavey  ;  T. Sarkisian  ;  G. Grateau  ;  E. S. Alnemri  ;  S. Amselem 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.105(5) : 1614-1619, 2008 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2008
MeSH
Amino Acid Sequence ; Base Sequence ; Child ; Codon, Nonsense/genetics ; Familial Mediterranean Fever/genetics* ; Female ; Humans ; Intracellular Signaling Peptides and Proteins/genetics* ; Intracellular Signaling Peptides and Proteins/physiology ; Male ; Molecular Sequence Data ; Mutation ; NF-kappa B/metabolism ; Pedigree ; RNA Splice Sites ; RNA Splicing/genetics ; Sequence Analysis, DNA
Keywords
genetics ; Mendelian disorder ; NLRP ; autoinflammatory disorder ; CATERPILLER
Abstract
NALP proteins, also known as NLRPs, belong to the CATERPILLER protein family involved, like Toll-like receptors, in the recognition of microbial molecules and the subsequent activation of inflammatory and immune responses. Current advances in the function of NALPs support the recently proposed model of a disease continuum bridging autoimmune and autoinflammatory disorders. Among these diseases, hereditary periodic fevers (HPFs) are Mendelian disorders associated with sequence variations in very few genes; these variations are mostly missense mutations whose deleterious effect, which is particularly difficult to assess, is often questionable. The growing number of identified sporadic cases of periodic fever syndrome, together with the lack of discriminatory clinical criteria, has greatly hampered the identification of new disease-causing genes, a step that is, however, essential for appropriate management of these disorders. Using a candidate gene approach, we identified nonambiguous mutations in NALP12 (i.e., nonsense and splice site) in two families with periodic fever syndromes. As shown by means of functional studies, these two NALP12 mutations have a deleterious effect on NF-kappaB signaling. Overall, these data identify a group of HPFs defined by molecular defects in NALP12, opening up new ways to manage these disorders. The identification of these first NALP12 mutations in patients with autoinflammatory disorder also clearly demonstrates the crucial role of NALP12 in inflammatory signaling pathways, thereby assigning a precise function to this particular member of an emerging family of proteins whose putative biological properties are currently inferred essentially through in vitro means.
Files in This Item:
T200895725.pdf Download
DOI
10.1073/pnas.0708616105
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Yu, Je Wook(유제욱) ORCID logo https://orcid.org/0000-0001-5943-4071
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108651
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links