TY - JOUR
T1 - A Novel Biallelic STING1 Gene Variant Causing SAVI in Two Siblings
AU - Alghamdi, Malak Ali
AU - Mulla, Jaazeel
AU - Saheb Sharif-Askari, Narjes
AU - Guzmán-Vega, Francisco J.
AU - Arold, Stefan T.
AU - Abd-Alwahed, Mervat
AU - Alharbi, Nasser
AU - Kashour, Tarek
AU - Halwani, Rabih
N1 - KAUST Repository Item: Exported on 2021-02-02
Acknowledgements: The authors extend their appreciation to the Deputyship for Research & Innovation, “Ministry of Education” in Saudi Arabia for funding this research work through the project number IFKSURG-2020-125.
PY - 2021/1/8
Y1 - 2021/1/8
N2 - STING-associated vasculopathy of infantile-onset (SAVI) is one of the newly identified types of interferonopathies. SAVI is caused by heterozygous gain-of-function mutations in the STING1. We herein report for the first time a homozygous variant in the STING1 gene in two siblings that resulted in constitutive activation of STING gene and the SAVI phenotype. Exome sequencing revealed a novel homozygous NM_198282.3: c.841C>T; p.(Arg281Trp) variant in exon 7 of the STING1 gene. The variant segregated in the family to be homozygous in all affected and either heterozygous or wild type in all healthy. Computational structural analysis of the mutants revealed changes in the STING protein structure/function. Elevated serum beta-interferon levels were observed in the patients compared to the control family members. Treatment with Janus kinase inhibitor (JAK-I) Ruxolitinib suppressed the inflammatory process, decreased beta-interferon levels, and stopped the progression of the disease.
AB - STING-associated vasculopathy of infantile-onset (SAVI) is one of the newly identified types of interferonopathies. SAVI is caused by heterozygous gain-of-function mutations in the STING1. We herein report for the first time a homozygous variant in the STING1 gene in two siblings that resulted in constitutive activation of STING gene and the SAVI phenotype. Exome sequencing revealed a novel homozygous NM_198282.3: c.841C>T; p.(Arg281Trp) variant in exon 7 of the STING1 gene. The variant segregated in the family to be homozygous in all affected and either heterozygous or wild type in all healthy. Computational structural analysis of the mutants revealed changes in the STING protein structure/function. Elevated serum beta-interferon levels were observed in the patients compared to the control family members. Treatment with Janus kinase inhibitor (JAK-I) Ruxolitinib suppressed the inflammatory process, decreased beta-interferon levels, and stopped the progression of the disease.
UR - http://hdl.handle.net/10754/667137
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2020.599564/full
UR - http://www.scopus.com/inward/record.url?scp=85099750110&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.599564
DO - 10.3389/fimmu.2020.599564
M3 - Article
C2 - 33488593
SN - 1664-3224
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
ER -