ZFIN ID: ZDB-PUB-150203-2
Functional variants of POC5 identified in patients with idiopathic scoliosis
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.
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.
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.