Synteny-defined candidate genes for congenital and idiopathic scoliosis

Idiopathic scoliosis (IS) is a common but poorly understood syndrome. Conge nital scoliosis (CS) is less common but comparably unexplored, Previous stu dies suggest that each has a significant genetic component, However, the oc currence of scoliosis in the presence of other hereditary connective tissue syndromes raises the possibility that IS and CS are in fact a heterogeneou s group of disorders with varied pathogenetic mechanisms, Mouse mutations h ave proven informative in identifying genes that are important in the devel opment of the musculoskeletal system and provided important mechanistic ins ights regarding their roles in human disease. We sought to identify candida te genes for human IS and CS by reviewing mouse mutations with phenotypes a ffecting the axial skeleton. We performed a systematic review using the Mou se Genome Database (MGD), the Genome Database (GDB), and the Online Mendeli an Inheritance in Man (OMIM) world-wide-web sites with additional searches performed based on the results of this initial search. We identified approx imately 400 mouse mutations, reviewed approximately 250 of these for verteb ral phenotypes, assessed 45 of these for synteny conservation between mouse and man, and identified 28 mouse mutations for which 29 credible candidate s for human scoliosis could be identified based on mouse phenotypic and map ping data. For each of these, we have synthesized information about the mou se mutant phenotype, mapping data, information regarding molecular pathogen esis when a specific causative gene has been identified, and information re garding plausible candidates based on map position when the causative gene has not been identified, Among these were three loci for which the mutant g ene had been identified and the human homologue was known, Some of the mous e mutants have phenotypes similar to human syndromes. (C) 1999 Wiley-Liss, Inc.