## 1 Introduction  
Generalized pustular psoriasis (GPP; MIM 614204), the most severe form of all the psoriatic diseases, is a rare multisystemic autoinflammatory disease characterized by episodes of acute generalized erythema and scaling developed with the spread of numerous sterile pustules [1]. Patients with GPP may have pustular skin reactions similar to those seen in individuals with adult-onset immunodeficiency syndrome (AOID) with anti-interferon-\(\gamma\) (IFN-\(\gamma\)) autoantibodies [1, 2]. AOID is an autoimmune disease characterized by an AIDS-like illness with abnormal IFN-\(\gamma\)/IL12 signaling. The clinical manifestations of patients affected with AOID resemble those in patients with inborn deficiencies of IFN-\(\gamma\) production or IFN-\(\gamma\)-response because IFN-\(\gamma\) has a non-redundant role in fighting mycobacterial infection [2, 3]. Patients with AOID generally present with signs and symptoms of aberrant cell-mediated immunity including recurrent and disseminated infection by mycobacteria with low virulence. Their clinical responses to anti-mycobacterial therapy are generally poor [4]. The majority of cases have skin involvement, including reactive skin disorders (82%) and infective skin diseases (45%), which are mostly neutrophic dermatoses [2, 5]. AOID is more prevalent in Thailand and Taiwan than the rest of the world [2], suggestive of a genetic predisposition in these populations. The age of onset of AOID is around 30-50 years old [2]. AOID shares skin manifestations with GPP, including the pustular reaction, suggestive of shared pathogenic mechanisms [5]. To the best of our knowledge, however, AOID and GPP have not been reported in the same subjects or within the same families. Regarding genetic susceptibility, HLA-DRB1*15:01, DRB1*16:02 and HLA-DQB1*05:01, DQB1*05:02 alleles have been reported to be associated with AOID in the Thai population [4], whereas variants in other genes including _IL36 RN_, _CARD14_, _IL1 RN_, _AP153_, _MPO_, _TNIP1_, and _SERPINA3_ have been reported to be associated with GPP [1], [[PERSON] et al., 2021]. Recently, we reported heterozygous variants in _SERPINA3_ and _SERPINA1_ in patients with AOID [6] and GPP [7], respectively. Transforming growth factor beta (TGFB) signaling has important roles in regulating a variety of cellular processes as well as the formation of extracellular matrix. TGFB1 has an anti-proliferative role in the epidermis [8]. Mechanistically, TGFB1 ligand binds first to TGFBR2 (TRANSFORMING GROWTH FACTOR-BETA RECEPTOR, TYPE II; MIM 190182), followed by the interaction and phosphorylation of a glycine-serine-rich domain of TGFBR1 (TRANSFORMING GROWTH FACTOR-BETA RECEPTOR, TYPE I; MIM 190181) to form an activated ligand-receptor complex. Both TGFBR1 and TGFBR2 are transmembrane serine/threonine kinases. Transphosphorylation of the glycine-serine-rich domain of TGFBR1 by TGFBR2 switches the glycine-serine-rich domain from the binding site for the inhibitor FKBP12 to a binding site for the R-Smad substrate, initiating Smad-dependent signal transduction [9]. TGFBR2 is constitutively active [9], and its expression is dramatically decreased or absent in psoriatic skin [8]. Variants in _TGFBR2_ have been reported to be associated with [PERSON] syndrome 2 (MIM 610168), colorectal cancer-hereditary nonpolyosis type 6 (MIM 614331), and esophageal cancer (MIM 133239) [10, 11]. Variants in _TGFBR2_ have not previously been reported to be associated with GPP and AOID. Previously, a genetic variant in SERPINA1 was found to be a predisposing factor in the presentation of both GPP and AOID [7]. Although TGFBR2 has not previously been reported to be associated with GPP and AOID, the expression of TGFBR2 is notably decreased or absent in psoriatic skin [8]. Therefore, we hypothesized that genetic variants in TGFBR2 might also predispose some patients in our cohort to GPP and AOID. Here, we report four Thai patients, two presenting with GPP and two AOID with a pustular skin reaction, who carried the same heterozygous frameshift mutation in TGFBR2.