Cargando…

A Novel Rare Missense Variation of the NOD2 Gene: Evidences of Implication in Crohn’s Disease

The NOD2 gene, involved in innate immune responses to bacterial peptidoglycan, has been found to be closely associated with Crohn’s Disease (CD), with an Odds Ratio ranging from 3–36. Families with three or more CD-affected members were related to a high frequency of NOD2 gene variations, such as R7...

Descripción completa

Detalles Bibliográficos
Autores principales: Frade-Proud’Hon-Clerc, Sara, Smol, Thomas, Frenois, Frédéric, Sand, Olivier, Vaillant, Emmanuel, Dhennin, Véronique, Bonnefond, Amélie, Froguel, Philippe, Fumery, Mathurin, Guillon-Dellac, Nathalie, Gower-Rousseau, Corinne, Vasseur, Francis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412783/
https://www.ncbi.nlm.nih.gov/pubmed/30769939
http://dx.doi.org/10.3390/ijms20040835
_version_ 1783402685504946176
author Frade-Proud’Hon-Clerc, Sara
Smol, Thomas
Frenois, Frédéric
Sand, Olivier
Vaillant, Emmanuel
Dhennin, Véronique
Bonnefond, Amélie
Froguel, Philippe
Fumery, Mathurin
Guillon-Dellac, Nathalie
Gower-Rousseau, Corinne
Vasseur, Francis
author_facet Frade-Proud’Hon-Clerc, Sara
Smol, Thomas
Frenois, Frédéric
Sand, Olivier
Vaillant, Emmanuel
Dhennin, Véronique
Bonnefond, Amélie
Froguel, Philippe
Fumery, Mathurin
Guillon-Dellac, Nathalie
Gower-Rousseau, Corinne
Vasseur, Francis
author_sort Frade-Proud’Hon-Clerc, Sara
collection PubMed
description The NOD2 gene, involved in innate immune responses to bacterial peptidoglycan, has been found to be closely associated with Crohn’s Disease (CD), with an Odds Ratio ranging from 3–36. Families with three or more CD-affected members were related to a high frequency of NOD2 gene variations, such as R702W, G908R, and 1007fs, and were reported in the EPIMAD Registry. However, some rare CD multiplex families were described without identification of common NOD2 linked-to-disease variations. In order to identify new genetic variation(s) closely linked with CD, whole exome sequencing was performed on available subjects, comprising four patients in two generations affected with Crohn’s disease without R702W and G908R variation and three unaffected related subjects. A rare and, not yet, reported missense variation of the NOD2 gene, N1010K, was detected and co-segregated across affected patients. In silico evaluation and modelling highlighted evidence for an adverse effect of the N1010K variation with regard to CD. Moreover, cumulative characterization of N1010K and 1007fs as a compound heterozygous state in two, more severe CD family members strongly suggests that N1010K could well be a new risk factor involved in Crohn’s disease genetic susceptibility.
format Online
Article
Text
id pubmed-6412783
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-64127832019-04-05 A Novel Rare Missense Variation of the NOD2 Gene: Evidences of Implication in Crohn’s Disease Frade-Proud’Hon-Clerc, Sara Smol, Thomas Frenois, Frédéric Sand, Olivier Vaillant, Emmanuel Dhennin, Véronique Bonnefond, Amélie Froguel, Philippe Fumery, Mathurin Guillon-Dellac, Nathalie Gower-Rousseau, Corinne Vasseur, Francis Int J Mol Sci Article The NOD2 gene, involved in innate immune responses to bacterial peptidoglycan, has been found to be closely associated with Crohn’s Disease (CD), with an Odds Ratio ranging from 3–36. Families with three or more CD-affected members were related to a high frequency of NOD2 gene variations, such as R702W, G908R, and 1007fs, and were reported in the EPIMAD Registry. However, some rare CD multiplex families were described without identification of common NOD2 linked-to-disease variations. In order to identify new genetic variation(s) closely linked with CD, whole exome sequencing was performed on available subjects, comprising four patients in two generations affected with Crohn’s disease without R702W and G908R variation and three unaffected related subjects. A rare and, not yet, reported missense variation of the NOD2 gene, N1010K, was detected and co-segregated across affected patients. In silico evaluation and modelling highlighted evidence for an adverse effect of the N1010K variation with regard to CD. Moreover, cumulative characterization of N1010K and 1007fs as a compound heterozygous state in two, more severe CD family members strongly suggests that N1010K could well be a new risk factor involved in Crohn’s disease genetic susceptibility. MDPI 2019-02-15 /pmc/articles/PMC6412783/ /pubmed/30769939 http://dx.doi.org/10.3390/ijms20040835 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Frade-Proud’Hon-Clerc, Sara
Smol, Thomas
Frenois, Frédéric
Sand, Olivier
Vaillant, Emmanuel
Dhennin, Véronique
Bonnefond, Amélie
Froguel, Philippe
Fumery, Mathurin
Guillon-Dellac, Nathalie
Gower-Rousseau, Corinne
Vasseur, Francis
A Novel Rare Missense Variation of the NOD2 Gene: Evidences of Implication in Crohn’s Disease
title A Novel Rare Missense Variation of the NOD2 Gene: Evidences of Implication in Crohn’s Disease
title_full A Novel Rare Missense Variation of the NOD2 Gene: Evidences of Implication in Crohn’s Disease
title_fullStr A Novel Rare Missense Variation of the NOD2 Gene: Evidences of Implication in Crohn’s Disease
title_full_unstemmed A Novel Rare Missense Variation of the NOD2 Gene: Evidences of Implication in Crohn’s Disease
title_short A Novel Rare Missense Variation of the NOD2 Gene: Evidences of Implication in Crohn’s Disease
title_sort novel rare missense variation of the nod2 gene: evidences of implication in crohn’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412783/
https://www.ncbi.nlm.nih.gov/pubmed/30769939
http://dx.doi.org/10.3390/ijms20040835
work_keys_str_mv AT fradeproudhonclercsara anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT smolthomas anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT frenoisfrederic anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT sandolivier anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT vaillantemmanuel anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT dhenninveronique anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT bonnefondamelie anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT froguelphilippe anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT fumerymathurin anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT guillondellacnathalie anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT gowerrousseaucorinne anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT vasseurfrancis anovelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT fradeproudhonclercsara novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT smolthomas novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT frenoisfrederic novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT sandolivier novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT vaillantemmanuel novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT dhenninveronique novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT bonnefondamelie novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT froguelphilippe novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT fumerymathurin novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT guillondellacnathalie novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT gowerrousseaucorinne novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease
AT vasseurfrancis novelraremissensevariationofthenod2geneevidencesofimplicationincrohnsdisease