A curve in the spine

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.

Published February 2, 2015, by Corinne Williams

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Functional variants of POC5 identified in patients with idiopathic scoliosis
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Published March 2, 2015; First published February 2, 2015
Citation Information: J Clin Invest. 2015;125(3):1124-1128. https://doi.org/10.1172/JCI77262.
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Categories: Brief Report Genetics

Functional variants of POC5 identified in patients with idiopathic scoliosis

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.

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

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