Generation of iPSCs from a Patient with the M694V Mutation in the Gene Associated with Familial Mediterranean Fever and Their Differentiation into Macrophages.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the (Mediterranean FeVer) gene, located on chromosome 16 (16p13.3) and encoding the pyrin protein. Despite the existing data on mutations, the exact mechanism of their effect on the development of the pathological processes leading to the spontaneous and recurrent autoinflammatory attacks observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool to study the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs from an Armenian patient with FMF carrying the M694V, p.(Met694Val) (c.2080A>G, rs61752717) pathogenic mutation in exon 10 of the gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. We found that the morphology of macrophages derived from iPSCs of a patient with the mutation significantly differed from that of macrophages derived from iPSCs of a healthy donor carrying the wild-type gene.