Clinical, immunological, and genetic findings
The patient is a 10-year-old girl born to healthy non-consanguineous
Spanish parents. She presented with oral thrush at the age of 12 months.
Whilst topical treatment with miconazole failed, she responded to
systemic oral fluconazole therapy. Thrush recurrence (every three to
four months) due to C. albicans prompted referral to our
immunodeficiency clinic when she was 6 years old. Other clinical
manifestations included persistent angular cheilitis with scaring,
recurrent wheezing, intermittent skin alterations such as eczema and
marked reactions to insect bites (Figure 2A) . In addition, she
suffered from two episodes of extensive impetigo secondary to local
fungal infections (Figure 2A) . So far, she has not experienced
invasive infections, scalp lesions, folliculitis, or blepharitis.
Physical examination including growth and weight was normal. There were
no facial, dental, or skeletal abnormalities. A full blood count, basic
immunology work-up including extended lymphocyte immunophenotyping and
immunoglobulin levels as well as serum INF-γ levels over the last 4
years were normal for age apart from mildly elevated IgE levels(supplementary Table 2) . Targeted NGS sequencing revealed a
heterozygous variant (c.1363C>A/p.D451G) of STAT1inherited from her father; both mother and sister were WT. In addition,
the patient carries private compound heterozygous variants ofTRAF3IP2 : c.1325A>G (p.D451G), inherited from her
mother, and c.1335delA (resulting in a frameshift and a premature stop
codon p.K454fs11*) inherited from her father, as did her sister
(Figure 2B-2C) .