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.
FIGURES
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.
ADDITIONAL INFORMATION