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

Area of Science:

• Genetics
• Immunology
• Rare Diseases

Background:

• Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency with autosomal dominant (AD-HIES) and recessive (AR-HIES) forms.
• Mutations in STAT3 and DOCK8 are the primary genetic causes for AD-HIES and AR-HIES, respectively.
• The full spectrum of HIES mutations and their pathogenic mechanisms require further elucidation, particularly in underrepresented populations.

Observation:

• Two Chinese pediatric patients presented with clinical symptoms consistent with HIES.
• Diagnostic workup included clinical evaluation, laboratory findings, and targeted next-generation sequencing (NGS).

Findings:

• NGS identified a novel heterozygous 15-bp deletion in STAT3 (c.1960_1974del) in one patient.
• A recurrent missense mutation in STAT3 (c.1144C>T, p.R382W) was identified in the second patient.
• Both patients responded well to cefaclor treatment for skin infections and remained infection-free during a 6-month follow-up.

Implications:

• These findings expand the known spectrum of STAT3 mutations associated with autosomal dominant HIES.
• Targeted NGS is a valuable tool for the accurate diagnosis of genetic immunodeficiencies like HIES.
• Understanding the genetic basis of HIES is crucial for improved diagnosis and management of affected individuals.