Idiopathic scoliosis (IS) is a relatively common spinal deformity that is characterized by lateral curvature of the spine. Many lines of evidence suggest a hereditary component to the disease, as it is often present in multiple family members; however, there has not been a definitive identification of an IS-inducing gene. Shunmoogum Patten and colleagues at the University of Montréal evaluated a large family with multiple members affected with IS and identified a variant of the gene encoding the centriole protein POC5 that was present in individuals with IS. Moreover, this variant and was present in other families and individuals with IS. The authors also identified 2 additional POC5 variants in additional IS cases. Expression of any one of these IS-associated POC5 variants in a zebrafish model resulted in spine deformity without an effect on other skeletal structures. Together, the results of this study indicate that POC5 mutations underlie some occurrences of IS. The accompanying movie shows a 3D reconstruction of a microCT scan of the vertebral column of a zebrafish expressing an IS-associated POC5 variant. Note the curvature and vertical rotation.
Idiopathic scoliosis (IS) is a spine deformity that affects approximately 3% of the population. The underlying causes of IS are not well understood, although there is clear evidence that there is a genetic component to the disease. Genetic mapping studies suggest high genetic heterogeneity, but no IS disease-causing gene has yet been identified. Here, genetic linkage analyses combined with exome sequencing identified a rare missense variant (p.A446T) in the centriolar protein gene
Shunmoogum A. Patten, Patricia Margaritte-Jeannin, Jean-Claude Bernard, Eudeline Alix, Audrey Labalme, Alicia Besson, Simon L. Girard, Khaled Fendri, Nicolas Fraisse, Bernard Biot, Coline Poizat, Amandine Campan-Fournier, Kariman Abelin-Genevois, Vincent Cunin, Charlotte Zaouter, Meijiang Liao, Raphaelle Lamy, Gaetan Lesca, Rita Menassa, Charles Marcaillou, Melanie Letexier, Damien Sanlaville, Jerome Berard, Guy A. Rouleau, Françoise Clerget-Darpoux, Pierre Drapeau, Florina Moldovan, Patrick Edery