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A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis. Bone

Department of Pediatrics, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA.
Bone (Impact Factor: 4.46). 01/2006; 38(1):41-7. DOI: 10.1016/j.bone.2005.07.009
Source: PubMed

ABSTRACT Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder that primarily affects bone but is often accompanied by inflammation of the skin and/or gastrointestinal tract. The etiology is unknown but evidence suggests a genetic component to disease susceptibility. Although most cases of CRMO are sporadic, there is an autosomal recessive syndromic form of the disease, called Majeed syndrome, which is due to homozygous mutations in LPIN2. In addition, there is a phenotypically similar mouse, called cmo (chronic multifocal osteomyelitis) in which the disease is inherited as an autosomal recessive disorder. The cmo locus has been mapped to murine chromosome 18. In this report, we describe phenotypic abnormalities in the cmo mouse that include bone, cartilage and skin inflammation. Utilizing a backcross breeding strategy, we refined the cmo locus to a 1.3 Mb region on murine chromosome 18. Within the refined region was the gene pstpip2, which shares significant sequence homology to the PSTPIP1. Mutations in PSTPIP1 have been shown to cause the autoinflammatory disorder PAPA syndrome (pyogenic arthritis, pyoderma gangrenosum and acne). Mutation analysis, utilizing direct sequencing, revealed a single base pair change c.293T --> C in the pstpip2 gene resulting in a highly conserved leucine at amino acid 98 being replaced by a proline (L98P). No other mutations were found in the coding sequence of the remaining genes in the refined interval, although a 50 kb gap remains unexplored. These data suggest that mutations in pstpip2 may be the genetic explanation for the autoinflammatory phenotype seen in the cmo mouse.

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    • "Mouse CMO has been shown to be conveyed in an autosomal recessive manner. The PSTPIP2 gene on the mouse chromosome 18 has been recognized as the causative gene for CMO [14]. However, the PSTPIP2 gene resides on chromosome 18q12 in humans, while the responsible gene locus for sporadic CRMO cases is thought to dwell on chromosome 18q21-22, so it is unclear if the PSTPIP2 gene can be a causative agent in humans [15]. "
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    ABSTRACT: Chronic recurrent multifocal osteomyelitis (CRMO) is a diagnosis of exclusion primarily in children and adolescents. As part of the essential criteria for the diagnosis of CRMO, multifocal lesions must be identified. We present the case of an 11-year-old boy with CRMO, whose diagnosis was facilitated by the use of whole body magnetic resonance imaging (WBMR), but not isotope bone scanning.
    Orthopaedics & Traumatology Surgery & Research 05/2012; 98(4):461-4. DOI:10.1016/j.otsr.2012.02.006 · 1.17 Impact Factor
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    • "The underlying defect and the pathogenesis of CRMO are largely unknown. Based on the finding that spontaneous recessive mutations in Pstpip2 (a murine gene encoding a protein homologous to the PAPA-pyogenic arthritis, pyoderma gangrenosum, and acne-syndrome protein PSTPIP1) cause, in the cmo mouse model, an autoinflammatory bone disease most closely resembling CRMO [3] [4], the later is considered as an autoinflammatory disorder [5]. Despite the fact that the human PSTPIP2 gene is encoded within a genomic interval found to be associated with sporadic CRMO by transmission disequilibrium testing [6], no PST- PIP2 mutations have been as yet identified in CRMO syn- drome. "
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    ABSTRACT: We report a case of a 13-year-old girl with chronic recurrent multifocal osteomyelitis (CRMO) who developed severe arthritis in four different joints within the first year from the onset of the disease. Her multiple vertebrae lesions showed significant amelioration after a 2-month treatment with prednisolone. In parallel, the initial severe symmetrical arthritis of both knees showing overt synovitis and joint effusion, in the absence of lesions in the metaphyses of the femur or the tibia, responded remarkably well in intra-articular triamcinolone hexacetonide injections. However, upon discontinuation of prednisolone, the patient developed severe arthritis of her right ankle and the proximal interphalangeal joint of her right middle finger. Thus, prednisolone was reinitiated combined with methotrexate, and the patient went into remission, which persists one year after prednisolone tapering. The appearance of arthritis in both knees in the absence of bone lesions and the emergence of severe arthritis of the ankle after remission of spinal bone lesions suggest that CRMO and juvenile idiopathic arthritis may coexist and be causally related.
    12/2011; 2011(4):210795. DOI:10.1155/2011/210795
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    • "L'hypothèse d'une implication des germes cutanés tels que Staphylococcus aureus, Mycoplasma hominis ou Propionibacterium acnes dans l'induction d'antigènes potentiels reste incertaine. Les facteurs génétiques sont étudiés sur le modèle de souris atteintes d'ostéomyélite inflammatoire similaire à l'OMCR sur le plan histologique, et présentant une mutation du gène de la murine PSTPIP [5] [6]. La présentation clinique de l'OMCR n'est pas spécifique : les patients s'adressent en général pour un syndrome polyalgique diffus avec oedème du site atteint. "
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