Heterozygous Pathogenıc Masp2 Varıant Assocıated Wıth Infantıle Gıant Cell Hepatıtıs Wıth Autoımmune Haemolytıc Anaemıa In A Chıld

Objective: Infantile giant cell hepatitis with autoimmune hae molytic anaemia (GCH-AHA) is a rare disease characterised by giant cell and autoimmune haemolysis. The pathogenic mecha nisms involve several factors, including genetic and immunolog ical 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 GCH AHA. An in-house data analysis pipeline was applied to deter mine 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-phe notype correlations. Further investigations into the lectin path way's detailed activation and its impact on GCH-AHA pathogen esis are warranted for a comprehensive understanding of the disease mechanisms.