| CRMO is a chronic inflammatory disease of unknown etiology. It primarily affects children and results in recurrent fever and the development of multiple inflammatory bone lesions. It is frequently seen in association with other, more common, inflammatory disorders such as psoriasis, inflammatory bowel disease and cutaneous pustulosis making it a particularly interesting disorder to study. There are reports of affected siblings in the literature and published evidence for a susceptibility locus for CRMO on human chromosome 18q suggesting a genetic component to its etiology. In addition, there is a syndromic, autosomal recessive disorder, called Majeed syndrome, in which CRMO is a major clinical feature. The genetic basis of CRMO is further supported by the existence of a similar disorder in the mouse (cmo, chronic multifocal osteomyelitis) resulting from a spontaneous mutation that is inherited as an autosomal recessive trait. In collaboration with Dr. Hatem El-Shanti in the Division of Medical Genetics, we are in the process of dissecting the genetic basis of CRMO utilizing all 3 available models. First, the El-Shanti lab has recently demonstrated that Majeed Syndrome, a syndromic form of CRMO, is caused by defects in the LPIN2 gene. Second, my laboratory has recently identified the gene defect in the cmo mouse and are currently performing experiments to determine the immunologic abnormalities in these mice. Third, we (El-Shanti and Ferguson) are collecting DNA from patients with sporadic (non-syndromic) CRMO to see if we can determine the gene defect(s) in these patients. The goal of this research is to understand the genetic basis of chronic, non-infectious osteomyelitis. Knowledge about the gene defect(s) present in CRMO may aid in the understanding of the pathways of inflammation involved, not only in CRMO, but also in the inflammatory disorders that frequently accompany this disorder such as psoriasis and inflammatory bowel disease. |