Hyper IgE syndrome associated with novel and recurrent STAT3 mutations: Two case reports

RATIONALE: Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency presenting as two forms including autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES), which are mainly caused by mutations in STAT3 and DOCK8, respectively. To date, only about 500 cases have been reported worldwide including 37 cases in China. The spectrum and prevalence of mutations and molecular pathogenesis in HIES remain poorly understood. PATIENT CONCERNS: Here we reported two Chinese children presenting clinical manifestations of HIES. DIAGNOSIS: Based on medical history, clinical manifestations, and laboratory findings, a diagnosis of HIES was made for both children. Targeted next-generation sequencing (NGS) identified a novel heterozygous deletion of 15 bp (c.1960_1974del, p.G654_D658del or alternatively c.1966_1980del, and p.G656_D660del), and a recurrent missense mutation (c.1144C>T, p.R382W) in STAT3 in the two patients, respectively. INTERVENTIONS: The two patients have been given the successful treatment of skin infections with cefaclor. OUTCOMES: Both patients have been under follow-up for more than 6 months, with no signs of recurrent infections. LESSONS: Our results extend the spectrum of STAT3 mutations associated with ADHIES and highlight the value of targeted NGS in confirming diagnosis of genetic disorders.