Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 125, Issue 3, Pages 1124-1128Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI77262
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Funding
- CHU Sainte-Justine
- Foundation of Stars
- Canadian Institutes of Health Research (CIHR)
- Fondation Yves Cotrel-Institut de France
- Faculte de Medecine Dentaire, the Universite de Montreal, Fonds Ernest Charron
- Reseau de Recherche en Sante Buccodentaire et Osseuse (RSBO)
- CIHR
- French Ministry of Health
- Fondation Maladies Rares
- Hospices Civils de Lyon
- Inserm
- CNRS
- Lyon 1 University
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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.
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