A Novel Biallelic Gene Variant Causing SAVI in Two Siblings

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Jan 25

PMID 33488593

Citations 10

Authors

Malak Ali Alghamdi

Jaazeel Mulla

Narjes Saheb Sharif-Askari

Francisco J Guzman-Vega

Stefan T Arold

Mervat Abd-Alwahed

Nasser Alharbi

Tarek Kashour

Rabih Halwani

Affiliations

Soon will be listed here.

Abstract

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 . We herein report for the first time a homozygous variant in the in two siblings that resulted in constitutive activation of 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 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.

Citing Articles

A rare manifestation of STING-associated vasculopathy with onset in infancy: a case report.

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