Severe interstitial lung disease as the first manifestation of a STING1 variant in a familial case.

Abstract

STING-associated vasculopathy with onset in infancy (SAVI) is a very rare autosomal-dominant Mendelian autoinflammatory disease caused by heterozygous gain-of-function mutations in STING1. Reported carriers of a STING1 gain-of-function mutations are mostly symptomatic. Herein, we present a case study of an infant who presented with cyanosis, dyspnea, clubbing fingers, failure to thrive, and widespread interstitial changes, all consistent with interstitial lung disease (ILD); however, there was a notable lack of characteristic cutaneous features and recurrent fever. Whole-exome sequencing detected a pathogenic heterozygous mutation (p.Arg218Gln) in STING1. Intriguingly, this mutation was also present in her father (aged 32 years), whereas this carrier was healthy and without clinical symptoms. This study emphasizes the need to consider the possibility of SAVI in infants with ILD, even if they lack typical manifestations. Our study also underlines the possibility that carriers with STING gain-of-function mutations are clinically asymptomatic.