Akademik Veri Yönetim Sistemi
Istanbul Tip Fakultesi Dergisi, cilt.87, sa.4, ss.291-298, 2024 (ESCI)
Objective: Infantile giant cell hepatitis with autoimmune haemolytic anaemia (GCH-AHA) is a rare disease characterised by giant cell and autoimmune haemolysis. The pathogenic mechanisms involve several factors, including genetic and immunological components, particularly those related to the lectin pathway of the complement system. In this study, we aimed to identify possible germline variations in patients with GCH-AHA. Material and Method: Whole-exome sequencing (WES) was performed on a 6-month-old boy who was diagnosed with GCHAHA. An in-house data analysis pipeline was applied to determine familial segregation using Sanger sequencing. ELISA was used for MASP2 protein detection. Result: WES revealed a likely pathogenic heterozygous missense variant (p.(Cys618Tyr)) in the mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) gene. The MASP2 variant identified in the serine protease domain was predicted to disrupt disulphide bonds. In vitro assays showed decreased MASP2 levels in the patient and mother compared with controls, supporting the potential pathogenicity of the variant. Conclusion: This study highlighted the association between a novel MASP2 variant and GCH-AHA, emphasising the role of the lectin pathway in the pathogenesis of this rare disorder. The variable expressivity and incomplete penetrance observed in MASP2 deficiency underscore the complexity of genotype-phenotype correlations. Further investigations into the lectin pathway's detailed activation and its impact on GCH-AHA pathogenesis are warranted for a comprehensive understanding of the disease mechanisms.