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07.13 A case of sting-associated vasculopathy with onset in infancy (savi) in a young adult male with a novel tmem173 gene mutation
  1. Evangelia Zampeli1,
  2. Aglaia G Vakrakou1,
  3. Anastasios E Germenis2,
  4. Clio P Mavragani3,
  5. Haralampos M Moutsopoulos1,
  6. Menelaos N Manoussakis1
  1. 1Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  2. 2Department of Immunology and Histocompatibility School of Medicine, University of Thessaly, Greece
  3. 3Department of Physiology, Medical school, National and Kapodistrian University of Athens, Athens, Greece

Abstract

The type-I interferonopathies comprise a recently recognised group of diseases characterised by an up-regulation of type-I interferon signalling. Autosomal dominant mutations in TMEM173 gene, which encodes the stimulator of interferon genes (STING), have been described in children presenting with cutaneous vasculopathy and pulmonary inflammation, lately termed STING-associated vasculopathy with onset in infancy (SAVI). Herein, we present a case of a 18-years old male patient, who has suffered from cutaneous vasculopathy since early infancy and recently diagnosed severe interstitial lung disease, wherein a novel TMEM173 gene mutation was identified, most probably representing a not yet reported causative genetic defect for SAVI. The patient presented with fever, diffuse livedo reticularis, resorption of distal phalanges, nail dystrophy and scarred ears. He has been suffering since early infancy from intermittent febrile episodes, livedo reticularis, Raynaud’s phenomenon and cutaneous vasculopathy affecting the ears, the nose, the fingers and the toes. The patient has also severe interstitial lung disease (markedly affected pulmonary function tests along with diffuse honeycombing, reticular opacities and patchy ground-glass on high-resolution chest CT scan). Since infancy, repeated laboratory examinations were revealing elevated acute phase reactants with negative cultures for microbes. Despite receiving sequentially or in combination, all immunosuppressive agents the disease was progressing. The possibility of a type-I interferonopathy was raised and genetic analysis was performed, which revealed a heterozygous mutation in exon 6 of TMEM173 gene (p.Cys206Gly, c.616T>G, with estimated frequency <0.0008236%, considered probably damaging by bioinformatic tools; PolyPhen score 0.986). The occurrence of type-I interferon signature was also verified in the patient’s peripheral whole blood cells, as compared to age-matched healthy controls and compared to his parents and male sibling. We present this SAVI case for raising awareness aiming at early and accurate diagnosis of this new disease entity and because the mutation found in this patient is a newly identified mutation and not been todate registered in the relevant databases (dbSNP, NCBI, ENSEMBL).

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