In Silico Analysis and In-depth Assessment of a Female Patient with a Missense Mutation in the F12 Gene Associated with Hereditary Angioedema Symptoms: A Case Study

Abstract

Hereditary angioedema (HAE) is a complex genetic disorder characterized by recurrent episodes of localized skin and mucosal swelling, with potential life-threatening complications, particularly in the upper respiratory tract. While much is understood about the mutations behind HAE I-II types, the genetic landscape of type III remains complex. Our study provides a comprehensive exploration of an undiagnosed case of a 13-year-old female presenting with HAE symptoms. Despite undergoing thorough clinical evaluations including blood, immunochemical, coprological, and allergen tests, no correlations with allergies or HAE I-II types were observed. Leveraging whole-exome sequencing, a unique missense mutation in the F12gene (NC_000005.9: g.176831826 C > G, Ala207Pro) was identified in the patient's genetic profile, which she inherited from both parents. Subsequent comprehensive in silico analyses suggest this mutation could be a potent contributor to HAE's III type manifestation, notably in homozygous females. The data brought forth intricate relationships between age-related hormonal changes (estrogen fluctuations), specific genetic variance, and the multifaceted bradykinin pathway's involvement in HAE episodes. Significantly, the mutation's position within the EGF-like 2 domain hints at possible effects on protein structure, which might impact its structural stability and subsequent function. Advanced bioinformatics approaches greatly streamlined the identification and comprehension of this pathogenic mutation, demonstrating their invaluable role, especially in atypical cases. We believe that merging in silico methodologies with clinical observations offers a promising avenue for a comprehensive understanding of genetic disorders, emphasizing an integrated approach essential for the development of personalized diagnostic and treatment approaches for diseases such as HAE.