Functional variants of POC5 identified in patients with idiopathic scoliosis
Year: 2015
Type: article
Study design: Observational Study
Abstract: 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 POC5 that cosegregated with the disease in a large family with multiple members affected with IS. Subsequently, the p.A446T variant was found in an additional set of families with IS and in an additional 3 cases of IS. Moreover, POC5 variant p.A455P was present and linked to IS in one family and another rare POC5 variant (p.A429V) was identified in an additional 5 cases of IS. In a zebrafish model, expression of any of the 3 human IS-associated POC5 variant mRNAs resulted in spine deformity, without affecting other skeletal structures. Together, these findings indicate that mutations in the POC5 gene contribute to the occurrence of IS.
DOI: 10.1172/jci77262
Authors: 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
Institutions: CHU Sainte-Justine Research Center, Université de Montréal, Inserm, Université Paris Diderot, Institut Universitaire d'Hématologie, Hospices Civils de Lyon, Lyon 1 Université, Centre National de la Recherche Scientifique, Centre de Recherche en Neurosciences de Lyon, Montreal Neurological Institute and Hospital, McGill University, IntegraGen (France), Hôpital Necker-Enfants Malades, Institut des Maladies Génétiques Imagine, Université Paris Descartes
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2015216249