Dominant negative <i>ADA2</i> mutations cause ADA2 deficiency in heterozygous carriers.

ABSTRACT: Human ADA2 deficiency (DADA2) is an inborn error of immunity with a broad clinical phenotype which encompasses vasculopathy including livedo racemosa and lacunar strokes, as well as hemato-immunological features. Diagnosis is based on the combination of decreased serum ADA2 activity and the identification of biallelic deleterious alleles in the ADA2 gene. DADA2 carriers harbor a single pathogenic variant in ADA2 and are mostly considered healthy and asymptomatic. However, some DADA2 carriers present a phenotype compatible with DADA2. Here, we report ten patients from seven kindreds presenting with a phenotype indicative of DADA2, in whom only a single pathogenic variant (p.G47R, p.G47V, p.R169Q, p.H424N) was identified. To test whether being heterozygote for specific variants

SUBMITTER: Wouters M 

PROVIDER: S-EPMC11661335 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature