Variant
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
15 Jun 2023
15 Jun 2023
Historique:
pmc-release:
15
12
2023
medline:
16
6
2023
pubmed:
31
5
2023
entrez:
31
5
2023
Statut:
ppublish
Résumé
Disabling pansclerotic morphea (DPM) is a rare systemic inflammatory disorder, characterized by poor wound healing, fibrosis, cytopenias, hypogammaglobulinemia, and squamous-cell carcinoma. The cause is unknown, and mortality is high. We evaluated four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM. Genomic sequencing independently identified three heterozygous variants in a specific region of the gene that encodes signal transducer and activator of transcription 4 ( Genome sequencing revealed three novel heterozygous missense gain-of-function variants in Gain-of-function variants in
Sections du résumé
BACKGROUND
BACKGROUND
Disabling pansclerotic morphea (DPM) is a rare systemic inflammatory disorder, characterized by poor wound healing, fibrosis, cytopenias, hypogammaglobulinemia, and squamous-cell carcinoma. The cause is unknown, and mortality is high.
METHODS
METHODS
We evaluated four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM. Genomic sequencing independently identified three heterozygous variants in a specific region of the gene that encodes signal transducer and activator of transcription 4 (
RESULTS
RESULTS
Genome sequencing revealed three novel heterozygous missense gain-of-function variants in
CONCLUSIONS
CONCLUSIONS
Gain-of-function variants in
Identifiants
pubmed: 37256972
doi: 10.1056/NEJMoa2202318
pmc: PMC10392571
mid: NIHMS1911531
doi:
Substances chimiques
Janus Kinases
EC 2.7.10.2
Nitriles
0
Pyrazoles
0
Pyrimidines
0
ruxolitinib
82S8X8XX8H
STAT4 protein, human
0
Dermatologic Agents
0
Anti-Inflammatory Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2241-2252Subventions
Organisme : NIH HHS
ID : National Human Genome Research Institute, Intramur
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008806
Pays : United States
Organisme : Intramural NIH HHS
ID : ZID AR041180
Pays : United States
Organisme : NIH HHS
ID : UL1TR001442
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001442
Pays : United States
Organisme : NIH HHS
ID : National Institute of Arthritis and Musculoskeleta
Pays : United States
Organisme : NIAID NIH HHS
ID : UH2 AI153029
Pays : United States
Organisme : NIH HHS
ID : S10 OD026929
Pays : United States
Organisme : NIH HHS
ID : UH2 AI153029
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM119850
Pays : United States
Organisme : NIGMS NIH HHS
ID : FI2 GM137942
Pays : United States
Organisme : NIH HHS
ID : Undiagnosed Diseases Network
Pays : United States
Organisme : NIH HHS
ID : R35 GM119850
Pays : United States
Organisme : NIH HHS
ID : T32GM8806
Pays : United States
Organisme : NIH HHS
ID : 1Fi2GM137942-01
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2023 Massachusetts Medical Society.
Références
Arch Dermatol. 1980 Feb;116(2):169-73
pubmed: 7356347
N Engl J Med. 2007 Sep 6;357(10):977-86
pubmed: 17804842
Am J Respir Crit Care Med. 2022 Mar 15;205(6):674-684
pubmed: 34851799
Pediatr Dermatol. 1999 May-Jun;16(3):245-7
pubmed: 10383790
Nat Genet. 2013 Nov;45(11):1284-92
pubmed: 24097067
Proc Natl Acad Sci U S A. 1994 May 24;91(11):4806-10
pubmed: 7545930
J Anat. 2001 May;198(Pt 5):581-9
pubmed: 11430697
Front Immunol. 2019 May 15;10:1093
pubmed: 31156640
Clin Immunol. 2020 Jan;210:108316
pubmed: 31770611
Cytogenet Cell Genet. 1997;77(3-4):207-10
pubmed: 9284918
Oncogene. 2000 May 15;19(21):2577-84
pubmed: 10851056
Oncogene. 2000 May 15;19(21):2638-44
pubmed: 10851063
Semin Immunopathol. 2019 May;41(3):327-337
pubmed: 30989321
Immunity. 2017 Feb 21;46(2):220-232
pubmed: 28228280
Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):E2776-E2785
pubmed: 28283662
Clin Exp Rheumatol. 2010 Sep-Oct;28(5 Suppl 61):S160-3
pubmed: 21044452
J Cell Physiol. 1983 Sep;116(3):345-51
pubmed: 6885932
J Clin Immunol. 2020 Nov;40(8):1065-1081
pubmed: 32852681
J Med Life. 2008 Jul-Sep;1(3):348-54
pubmed: 20108512
Int Immunopharmacol. 2020 Mar;80:106210
pubmed: 31972425
Semin Arthritis Rheum. 2015 Dec;45(3):284-93
pubmed: 26254121
Mol Cell. 2005 Mar 18;17(6):761-71
pubmed: 15780933
N Engl J Med. 2007 Oct 18;357(16):1608-19
pubmed: 17881745
Blood. 1999 Jan 1;93(1):15-24
pubmed: 9864141
Rheumatol Int. 2019 May;39(5):933-941
pubmed: 30838436
Immunity. 2000 Dec;13(6):805-15
pubmed: 11163196
Front Pharmacol. 2014 May 27;5:123
pubmed: 24904424
Cytokine. 2011 Aug;55(2):157-64
pubmed: 21536453
Br J Dermatol. 1997 Feb;136(2):293-4
pubmed: 9068760
Cell. 2022 Oct 13;185(21):3857-3876
pubmed: 36240739