Idiopathic scoliosis (IS) is a structural lateral curvature of the spine present in the late juvenile or adolescent period in otherwise normal individuals. Previous studies from a number of populations have suggested autosomal dominant, X-linked and/or multi-factorial modes of inheritance. As part of a large collaborative study of familial idiopathic scoliosis, 202 families (1198 individuals), each with at least two individuals with scoliosis, have been ascertained and clinically characterized. Phenotypes include degree of lateral curvature, curve type, age of onset and sex. A genome-wide screen was performed at the Center for Inherited Disease Research. The families were ranked based on the ratio of the likelihood of each family given an X-linked model relative to that of an autosomal model. The mode of inheritance for families at one end of the distribution was assumed to be X-linked, while that of the families at the other end of the distribution was assumed to be autosomal dominant. The families were stratified by mode of inheritance and by clinical subtype to reduce genetic heterogeneity and maximize the potential of finding the genes involved in this complex disorder. Evidence was found for linkage to a region on the X chromosome in a subset of these families. For the proportion of families that appeared most likely to be segregating an autosomal dominant form of the disorder, flanking makers were genotyped in five candidate regions (chromosomes 6, 9, 8, 16 and 17). In addition to this, flanking markers were genotyped in four candidate regions (chromosomes 2, 5, 6 and 13 on a group of 7 families with at least two individuals with kyphoscoliosis. Genotyping of SNP Ilumina marker panels on chromosomes 2, 5, 9, 13, 16, and X has been completed in an attempt to narrow the candidate regions in each of these subgroups. For the kyphoscoliosis families 74 SNPs in a 15 Mb region on chromosome 5 were genotyped using the Sequenome platform. This allowed us to narrow the region suggestive of linkage for kyphoscoliosis to a region less than 2 Mb long.
| Miller, Nancy H; Justice, Cristina M; Marosy, Beth et al. (2005) Identification of candidate regions for familial idiopathic scoliosis. Spine (Phila Pa 1976) 30:1181-7 |
| Justice, Cristina M; Miller, Nancy H; Marosy, Beth et al. (2003) Familial idiopathic scoliosis: evidence of an X-linked susceptibility locus. Spine (Phila Pa 1976) 28:589-94 |
