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

• Published in: Spine (Philadelphia, Pa. 1976) Pa. 1976), 2003-03, Vol.28 (6), p.589-594
• Main Authors: JUSTICE, Cristina M, MILLER, Nancy H, MAROSY, Beth, JUN ZHANG, WILSON, Alexander F
• Format: Article
• Language: English
• Subjects: Alleles; Biological and medical sciences; Chromosomes, Human, X - genetics; Diseases of the osteoarticular system; Diseases of the spine; Family; Female; Gene Frequency; Genetic Diseases, X-Linked - genetics; Genetic Linkage; Genetic Markers; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Lod Score; Male; Medical sciences; Penetrance; Scoliosis - genetics
• ISSN: 0362-2436; 1528-1159
• DOI: 10.1097/01.BRS.0000049940.39801.E6

A genomic screen and statistical linkage analysis of a large sample of families with individuals having idiopathic scoliosis was performed. To identify an X-linked susceptibility locus involved in the expression of familial idiopathic scoliosis. 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. 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. 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. 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.