Familial idiopathic scoliosis: evidence of an X-linked susceptibility locus

Abstract

Study design: A genomic screen and statistical linkage analysis of a large sample of families with individuals having idiopathic scoliosis was performed.

Objectives: To identify an X-linked susceptibility locus involved in the expression of familial idiopathic scoliosis.

Summary of background data: A large sample of families with individuals having idiopathic scoliosis (202 families; 1198 individuals) were diagnosed through physical examination and radiographic criteria, and genomic screening and genetic linkage analyses were performed.

Methods: Model-independent linkage analysis was used to screen genotyping data from 15 X-linked markers in 202 families (1198 individuals). Families were stratified based on the ratio of the likelihood of an X-linked dominant (XLD) inheritance model relative to that of an autosomal dominant (AD) model. Both model-independent and model-dependent linkage analyses were used to identify potential candidate regions.

Results: When the entire set of families were analyzed with model-independent methods, no result was significant at the 0.05 level for any of the markers. However, when the families were stratified based on the ratio of the likelihood of the X-linked dominant to autosomal dominant mode of inheritance, results from model-dependent linkage analysis of 15% of the families most likely to have X-linked dominant inheritance showed six adjacent markers with positive lod score values and a maximum lod score of 1.69 (theta = 0.2) at marker GATA172D05. A lod score of 2.23 at this same marker was found in a single family with six affected individuals.

Conclusion: The results suggest that a region on the X chromosome may be linked to the expression of familial idiopathic scoliosis in a subset of these families.