Allison J Cox1, Polly J Ferguson. 1. Division of Pediatric Rheumatology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Abstract
PURPOSE OF REVIEW: To summarize the current advances in our understanding or the genetic basis of nonbacterial osteomyelitis. RECENT FINDINGS: Chronic recurrent multifocal osteomyelitis (CRMO) is a complex genetic disorder. Past discoveries identified several single gene defects (LPIN2, Pstpip2 and IL1RN) that cause IL-1-mediated sterile multifocal osteomyelitis. Recently Lorden et al.'s studies show that LIPIN2 deficiency can activate the NLRP3 inflammasome through alterations in the function of P2X7 receptor providing evidence that Majeed syndrome is an NLRP3 inflammasomopathy. New gene discoveries include the identification of FBLIM1 as a CRMO susceptibility gene. Mutations in FBLIM1 were found in a consanguineous family with CRMO. Fblim1 is one of the most significantly differentially expressed gene in bone from chronic multifocal osteomyelitis (cmo) mice, plays a role in IL-10-driven anti-inflammatory responses, and is involved in the physiology of bone remodeling. Lastly, new data on the putative CRMO susceptibility locus on chromosome 18 is presented here. Using Sanger sequencing, rather than microsatellite analysis, the DS18S60 susceptibility region could not be replicated in a larger cohort. SUMMARY: CRMO occurs in humans, nonhuman primates, dogs and mice. There is a genetic component to disease but the genetic basis has only been identified for a small percentage of all cases.
PURPOSE OF REVIEW: To summarize the current advances in our understanding or the genetic basis of nonbacterial osteomyelitis. RECENT FINDINGS: Chronic recurrent multifocal osteomyelitis (CRMO) is a complex genetic disorder. Past discoveries identified several single gene defects (LPIN2, Pstpip2 and IL1RN) that cause IL-1-mediated sterile multifocal osteomyelitis. Recently Lorden et al.'s studies show that LIPIN2 deficiency can activate the NLRP3 inflammasome through alterations in the function of P2X7 receptor providing evidence that Majeed syndrome is an NLRP3 inflammasomopathy. New gene discoveries include the identification of FBLIM1 as a CRMO susceptibility gene. Mutations in FBLIM1 were found in a consanguineous family with CRMO. Fblim1 is one of the most significantly differentially expressed gene in bone from chronic multifocal osteomyelitis (cmo) mice, plays a role in IL-10-driven anti-inflammatory responses, and is involved in the physiology of bone remodeling. Lastly, new data on the putative CRMO susceptibility locus on chromosome 18 is presented here. Using Sanger sequencing, rather than microsatellite analysis, the DS18S60 susceptibility region could not be replicated in a larger cohort. SUMMARY: CRMO occurs in humans, nonhuman primates, dogs and mice. There is a genetic component to disease but the genetic basis has only been identified for a small percentage of all cases.
Authors: Stephanie Young; Namit Sharma; Jae Hoon Lee; Violeta Chitu; Volker Neumeister; Elisabeth Sohr; E Richard Stanley; Christian M Hedrich; Andrew W B Craig Journal: Dis Model Mech Date: 2019-08-20 Impact factor: 5.758
Authors: Adamo Pio d'Adamo; Anna Monica Bianco; Giovanna Ferrara; Martina La Bianca; Antonella Insalaco; Alberto Tommasini; Manuela Pardeo; Marco Cattalini; Francesco La Torre; Martina Finetti; Clotilde Alizzi; Gabriele Simonini; Virginia Messia; Serena Pastore; Rolando Cimaz; Marco Gattorno; Andrea Taddio Journal: Pediatr Rheumatol Online J Date: 2020-07-10 Impact factor: 3.054