Novel Majeed Syndrome-Causing LPIN2 Mutations Link Bone Inflammation to Inflammatory M2 Macrophages and Accelerated Osteoclastogenesis.
Farzana BhuyanAdriana A de JesusJacob MitchellEvgenia LeikinaRachel VanTriesRonit HerzogKaren B OnelAndrew OlerGina A Montealegre SanchezKim A JohnsonLena BichellBernadette MarreroLuis Fernandez De CastroYan HuangKatherine R CalvoMichael T CollinsSundar GanesanLeonid V ChernomordikPolly J FergusonRaphaela Goldbach ManskyPublished in: Arthritis & rheumatology (Hoboken, N.J.) (2021)
We report 2 novel compound heterozygous disease-causing mutations in LPIN2 in an American patient with Majeed syndrome. LPIN2 deficiency drives differentiation of proinflammatory M2-like macrophages and enhances intrinsic osteoclastogenesis. This provides a model for the pathogenesis of sterile osteomyelitis which differentiates Majeed syndrome from other IL-1-mediated autoinflammatory diseases.