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

Polly J Ferguson; Xinyu Bing; Mohammed A Vasef; Luis A Ochoa; Amar Mahgoub; Thomas J Waldschmidt; Lorraine T Tygrett; Annette J Schlueter; Hatem El-Shanti

doi:10.1016/j.bone.2005.07.009

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

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

Polly J Ferguson, Xinyu Bing, Mohammed A Vasef, Luis A Ochoa, Amar Mahgoub, Thomas J Waldschmidt, Lorraine T Tygrett, Annette J Schlueter and Hatem El-Shanti

Bone (New York, N.Y.), Vol.38(1), pp.41-47

2006

DOI: 10.1016/j.bone.2005.07.009

PMCID: PMC3726202

PMID: 16122996

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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.

Osteomyelitis

pstpip2

Psoriasis

Autoinflammatory

CRMO

Details

Title: Subtitle: A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis
Creators: Polly J Ferguson - Department of Pediatrics, 2532 JCP, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA
Xinyu Bing - Department of Pediatrics, 2532 JCP, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA
Mohammed A Vasef - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Luis A Ochoa - Department of Pediatrics, 2532 JCP, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA
Amar Mahgoub - Department of Pediatrics, 2532 JCP, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA
Thomas J Waldschmidt - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Lorraine T Tygrett - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Annette J Schlueter - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Hatem El-Shanti - Department of Pediatrics, 2532 JCP, Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Bone (New York, N.Y.), Vol.38(1), pp.41-47
DOI: 10.1016/j.bone.2005.07.009
PMID: 16122996
PMCID: PMC3726202
NLM abbreviation: Bone
ISSN: 8756-3282
eISSN: 1873-2763
Publisher: Elsevier Inc
Language: English
Date published: 2006
Academic Unit: Critical Care; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Medical Genetics and Genomics; Rheumatology, Allergy, and Immunology
Record Identifier: 9984046801402771

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