PUBLICATION
Functional variants of POC5 identified in patients with idiopathic scoliosis
- Authors
- Patten, S.A., Margaritte-Jeannin, P., Bernard, J.C., Alix, E., Labalme, A., Besson, A., Girard, S.L., Fendri, K., Fraisse, N., Biot, B., Poizat, C., Campan-Fournier, A., Abelin-Genevois, K., Cunin, V., Zaouter, C., Liao, M., Lamy, R., Lesca, G., Menassa, R., Marcaillou, C., Letexier, M., Sanlaville, D., Berard, J., Rouleau, G.A., Clerget-Darpoux, F., Drapeau, P., Moldovan, F., Edery, P.
- ID
- ZDB-PUB-150203-2
- Date
- 2015
- Source
- J. Clin. Invest. 125(3): 1124-8 (Journal)
- Registered Authors
- Drapeau, Pierre
- Keywords
- none
- MeSH Terms
-
- Animals
- Carrier Proteins/genetics*
- Case-Control Studies
- DNA Mutational Analysis
- Female
- Gene Frequency
- Genetic Association Studies
- Genetic Predisposition to Disease
- Humans
- Linkage Disequilibrium
- Male
- Mutation, Missense
- Pedigree
- Polymorphism, Single Nucleotide
- Scoliosis/genetics*
- Zebrafish
- PubMed
- 25642776 Full text @ J. Clin. Invest.
Citation
Patten, S.A., Margaritte-Jeannin, P., Bernard, J.C., Alix, E., Labalme, A., Besson, A., Girard, S.L., Fendri, K., Fraisse, N., Biot, B., Poizat, C., Campan-Fournier, A., Abelin-Genevois, K., Cunin, V., Zaouter, C., Liao, M., Lamy, R., Lesca, G., Menassa, R., Marcaillou, C., Letexier, M., Sanlaville, D., Berard, J., Rouleau, G.A., Clerget-Darpoux, F., Drapeau, P., Moldovan, F., Edery, P. (2015) Functional variants of POC5 identified in patients with idiopathic scoliosis. J. Clin. Invest.. 125(3):1124-8.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping