title: New disease gene location and high genetic heterogeneity in idiopathic scoliosis.
abstract: Idiopathic scoliosis (IS) is a spine disorder of unknown origin with 1.5-3% prevalence in the general population. Besides the large multifactorial-form sample of IS, 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 IS families compatible with dominant inheritance including 9-12 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 IS disease gene locus, as 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 IS 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 IS.
authors.affiliation: Hospices Civils de Lyon, Service de Cytogénétique Constitutionnelle, Bron, France. patrick.edery@chu-lyon.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Edery
authors.forename: Patricia
authors.initials: P
authors.lastname: Margaritte-Jeannin
authors.forename: Bernard
authors.initials: B
authors.lastname: Biot
authors.forename: Audrey
authors.initials: A
authors.lastname: Labalme
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Bernard
authors.forename: Joëlle
authors.initials: J
authors.lastname: Chastang
authors.forename: Behrouz
authors.initials: B
authors.lastname: Kassai
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Plais
authors.forename: Florina
authors.initials: F
authors.lastname: Moldovan
authors.forename: Francoise
authors.initials: F
authors.lastname: Clerget-Darpoux
mesh_terms: D002893:Chromosomes, Human, Pair 3; D002895:Chromosomes, Human, Pair 5; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D010375:Pedigree; D012600:Scoliosis / Q000235:genetics*