title: Chronic recurrent multifocal osteomyelitis (CRMO): evidence for a susceptibility gene located on chromosome 18q21.3-18q22.
abstract: Chronic recurrent multifocal osteomyelitis (CRMO) is characterised by recurrent inflammatory lesions in the metaphyses of long bones and usually affects children and adolescents. Similarity with an autosomal recessive mouse disorder (cmo, chronic multifocal osteomyelitis) prompted us to perform a family based association study with two markers on chromosome 18q in the region homologous to the cmo localisation of the mouse. We found a significant association of CRMO with a rare allele of marker D18S60, resulting in a haplotype relative risk (HRR) of 18. This suggests the existence of a gene in this region contributing in a significant manner to the aetiology of CRMO and concomitantly demonstrates evidence for a genetic basis of CRMO for the first time. This gene is different from RANK, which is mutated in familial expansile osteolysis (FEO), but not in CRMO. Mutation screening in RANK and the genes PIGN and KIAA1468 led to detection of two variants (one in RANK and one in PIGN), which are in linkage disequilibrium with the rare D18S60 allele, but not independently associated with CRMO.
authors.affiliation: Abteilung Medizinische Genetik der Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, Universität München, München, Germany. astrid.golla@uni-bonn.de
authors.forename: Astrid
authors.initials: A
authors.lastname: Golla
authors.forename: Annette
authors.initials: A
authors.lastname: Jansson
authors.forename: Juliane
authors.initials: J
authors.lastname: Ramser
authors.forename: Heide
authors.initials: H
authors.lastname: Hellebrand
authors.forename: Robert
authors.initials: R
authors.lastname: Zahn
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Bernd H
authors.initials: BH
authors.lastname: Belohradsky
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
mesh_terms: D000483:Alleles; D002887:Chromosomes, Human, Pair 18; D004252:DNA Mutational Analysis; D005192:Family Health; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation; D010019:Osteomyelitis / Q000235:genetics*; D010641:Phenotype
chemical_list: D005819:Genetic Markers