OBJECTIVES: Mollaret meningitis is a rare neurological condition characterized by recurrent episodes of aseptic meningitis and the presence of monocyte-derived atypical cells (Mollaret cells) in the cerebrospinal fluid. It is most frequently associated with herpes simplex virus type 2 infection; however, autoimmune and inflammatory disorders, including familial Mediterranean fever, have also been implicated in its pathogenesis. Here, we report an unreported MEFV variant in a patient with Mollaret meningitis and aim to evaluate its pathogenic relevance through in vitro functional analyses. METHODS: MEFV exon sequencing was performed in a patient with Mollaret meningitis who showed a favorable response to colchicine treatment. Functional analyses were conducted using THP-1 cell lines. THP-1 monocytes were transfected with the identified MEFV variant or a wild-type MEFV construct, and their effects on cell death and apoptosis-associated speck-like protein containing a Caspase Recruitment Domain (ASC) speck formation were evaluated, with or without UCN-01 stimulation. RESULTS: MEFV exon sequencing revealed a novel heterozygous L560F variant (c.1678C > T). Functional analyses demonstrated that, compared with the wild-type MEFV, the L560F variant induced more pronounced cell death and ASC speck formation following UCN-01 stimulation, supporting the pathogenic role of this novel variant. DISCUSSION: The L560F variant represents a novel MEFV variant with functional evidence supporting pathogenicity. The clinical effectiveness of colchicine in this patient further supports the pathogenicity of the L560F variant.
Handa et al. (Tue,) studied this question.