Abstract
Introduction
Idiopathic scoliosis is a spine disorder of unknown origin with a prevalence of 1·5-3% in the general population. Apart from the large multifactorial form sample of idiopathic scoliosis, there is a good evidence for the existence of a monogenic subgroup in which the disease is inherited in a dominant manner. However, results from published work suggest a strong heterogeneity in locations of the mutated genes.
Methods
With a high resolution genome-wide scan, we undertook linkage analyses in three large multigenerational families with idiopathic scoliosis compatible with dominant inheritance, including 11–12 affected members or obligate carriers.
Results
In two of these families, our results suggested intrafamilial genetic heterogeneity, whereas in the other we recorded a perfect marker disease co-segregation in two distinct chromosomal regions. We can state that one of these two locations is a novel idiopathic scoliosis disease gene locus, since the probability of having by chance this perfect co-segregation twice in the genome is very low (p=0·001). Lastly, in all three families studied, we excluded compatibility with linkage to the previously mapped dominant idiopathic scoliosis loci on chromosomes 19p13.3, 17p11.2, 9q34, 17q25, and 18q.
Conclusions
Our findings confirm that there is a high genetic heterogeneity within the subgroup of dominant forms of idiopathic scoliosis.
