New disease gene location and high genetic heterogeneity in idiopathic scoliosis

Patrick Edery (1) , Patricia Margaritte-Jeannin (1) , Bernard Biot (1) , Audrey Labalme (1) , Jean-Claude Bernard (1) , Joelle Chastang (1) , Behrouz Kassai (1) , Marie-Helene Plais (1) , Florina Moldovan (1) , Francoise Clerget-Darpoux (1)

1 Service de Cytogenetique Constitutionnelle

Idiopathic scoliosis is a spine disorder of unknown origin with 1.5-3% prevalence in the general population. Besides 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 literature suggest a strong heterogeneity in the locations of the mutated genes. Using a high resolution genome-wide scan, we performed linkage analyses in three large multigenerational idiopathic scoliosis families compatible with dominant inheritance including 9 to 12 affected members or obligate carriers. In two of these families, our results suggested intra-familial genetic heterogeneity whereas, in the other, we observed a perfect marker disease co-segregation in two regions at 3q12.1 and 5q13.3. We can state that one of these two locations is a novel idiopathic scoliosis disease gene locus, since the probability of having this perfect co-segregation twice by chance in the genome is very low (p=0.001). Lastly, in all three families studied, linkage to the previously mapped dominant idiopathic scoliosis loci on chromosomes 19p13.3, 17p11.2, 9q34, 17q25 and 18q is unlikely, confirming that there is a high genetic heterogeneity within the subgroup of dominant forms of idiopathic scoliosis.

Mots clés: Idiopathic scoliosis; complex disorder; genetic mapping

Patrick Edery, Patricia Margaritte-Jeannin, Bernard Biot, Audrey Labalme, Jean-Claude Bernard, et al.. New disease gene location and high genetic heterogeneity in idiopathic scoliosis. European Journal of Human Genetics, 2011, ⟨10.1038/ejhg.2011.31⟩. ⟨hal-00624160⟩