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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
JournalBone
Volume38
Issue number1
DOIs
Publication statusPublished - Jan 2006
Externally publishedYes

Fingerprint

Missense Mutation
Mutation
Chromosomes, Human, Pair 18
Genes
Inflammation
Bone and Bones
Skin
Disease Susceptibility
Sequence Homology
Chronic recurrent multifocal osteomyelitis
Proline
Leucine
Base Pairing
Cartilage
Breeding
Gastrointestinal Tract
Phenotype
Amino Acids

Keywords

  • Autoinflammatory
  • CRMO
  • Osteomyelitis
  • Psoriasis
  • pstpip2

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Ferguson, P. J., Bing, X., Vasef, M. A., Ochoa, L. A., Mahgoub, A., Waldschmidt, T. J., ... El-Shanti, H. (2006). A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis. Bone, 38(1), 41-47. https://doi.org/10.1016/j.bone.2005.07.009

A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis. / Ferguson, Polly J.; Bing, Xinyu; Vasef, Mohammed A.; Ochoa, Luis A.; Mahgoub, Amar; Waldschmidt, Thomas J.; Tygrett, Lorraine T.; Schlueter, Annette J.; El-Shanti, Hatem.

In: Bone, Vol. 38, No. 1, 01.2006, p. 41-47.

Research output: Contribution to journalArticle

Ferguson, PJ, Bing, X, Vasef, MA, Ochoa, LA, Mahgoub, A, Waldschmidt, TJ, Tygrett, LT, Schlueter, AJ & El-Shanti, H 2006, 'A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis', Bone, vol. 38, no. 1, pp. 41-47. https://doi.org/10.1016/j.bone.2005.07.009
Ferguson, Polly J. ; Bing, Xinyu ; Vasef, Mohammed A. ; Ochoa, Luis A. ; Mahgoub, Amar ; Waldschmidt, Thomas J. ; Tygrett, Lorraine T. ; Schlueter, Annette J. ; El-Shanti, Hatem. / A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis. In: Bone. 2006 ; Vol. 38, No. 1. pp. 41-47.
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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.",
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