PMC8552009_01
Clinical history previous to referral at our Center.
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The clinical history of the patient is summarized in  Figure 1 .
PMC8552009_02
PMC8552009_03
PMC8552009_04
Family tree.
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During the follow-up at our center, a next-generation sequencing (NGS) panel that included genes related to both congenital marrow failure and immune dysregulation syndromes was applied to our proband (II-1 in  Figure 2 ). Based on the American College of Medical Genetics and Genomics criteria, both variants are classified as having a "likely pathogenic" effect and, consistent with the autosomal recessive inheritance of DADA2 (OMIM#615688), they turned out to be inherited by her father and mother, respectively ( Figure 2 ). Both mutations were also found in the sister of the patient (II-2 in  Figure 2 ), who displayed a clinical history of polyarticular arthritis of the small joints of the hands, along with Raynaud's phenomenon, hip and knee arthralgia, mild leukopenia, and mild thrombocytopenia. After the result of the genetic test, a targeted immunological screening revealed hypogammaglobulinemia and increased values of DNT cells (2.5%) in the mother of the patient (I-2 in  Figure 2 ).
PMC8552009_05
Functional assay of ADA2 activity.
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As shown in  Figure 3 , no adenosine metabolites were detectable in our patient (Pt 1), thus suggesting a complete loss of enzymatic activity.