Familial idiopathic scoliosis: evidence of an X-linked susceptibility locus.
METHODS
A genomic screen and statistical linkage analysis of a large sample of families with individuals having idiopathic scoliosis was performed.


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


BACKGROUND
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.


CONCLUSIONS
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.
Justice
Cristina M
CM
Genometrics Section, NHGRI, National Institutes of Health, Baltimore, Maryland, USA.
Miller
Nancy H
NH
Marosy
Beth
B
Zhang
Jun
J
Wilson
Alexander F
AF
D000483:Alleles; D041321:Chromosomes, Human, X / Q000235:genetics; D005190:Family; D005260:Female; D005787:Gene Frequency; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D019683:Penetrance; D012600:Scoliosis / Q000235:genetics*
D005819:Genetic Markers