Mutation of POC1B in a Severe Syndromic Retinal Ciliopathy

Beck, B.B., Phillips, J.B., Bartram, M.P., Wegner, J., Thoenes, M., Pannes, A., Sampson, J., Heller, R., Göbel, H., Koerber, F., Neugebauer, A., Hedergott, A., Nürnberg, G., Nürnberg, P., Thiele, H., Altmüller, J., Toliat, M.R., Staubach, S., Boycott, K.M., Valente, E.M., Janecke, A.R., Eisenberger, T., Bergmann, C., Tebbe, L., Wang, Y., Wu, Y., Fry, A.M., Westerfield, M., Wolfrum, U., Bolz, H.J.
Human Mutation   35(10): 1153-62 (Journal)
Registered Authors
Phillips, Jennifer, Wang, Yang, Wegner, Jeremy, Westerfield, Monte
Joubert syndrome, LCA, POC1B, ciliopathy, zebrafish
MeSH Terms
  • Abnormalities, Multiple
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Cycle Proteins/genetics*
  • Cell Cycle Proteins/metabolism
  • Cerebellar Diseases/genetics*
  • Cerebellar Diseases/metabolism
  • Cerebellar Diseases/pathology
  • Cerebellum/abnormalities
  • Child
  • Cilia/metabolism
  • Cilia/ultrastructure
  • Eye Abnormalities/genetics*
  • Eye Abnormalities/metabolism
  • Eye Abnormalities/pathology
  • Gene Knockdown Techniques
  • Humans
  • Iraq
  • Kidney/pathology
  • Kidney Diseases, Cystic/genetics*
  • Kidney Diseases, Cystic/metabolism
  • Kidney Diseases, Cystic/pathology
  • Leber Congenital Amaurosis/genetics
  • Leber Congenital Amaurosis/metabolism
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Retina/abnormalities*
  • Retina/metabolism
  • Retina/pathology
  • Zebrafish
25044745 Full text @ Hum. Mutat.
We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA),Joubert syndrome (JBTS), and polycystic kidney disease.Targeted NGS for excluding mutations in known LCA and JBTS genes, homozygosity mapping and whole-exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B,a gene essential for ciliogenesis, basal body and centrosome integrity. In silico modeling suggested a requirement of p.Arg106 for formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer. Knockdown of Poc1b in zebrafish caused cystic kidneys and retinal degeneration with shortened and reduced photoreceptor connecting cilia, compatible with the human syndromic ciliopathy. A recent study describes homozygosity for p.Arg106ProPOC1B in a family with non-syndromic cone-rod dystrophy. The phenotype associated with homozygous p.Arg106ProPOC1B may thus be highly variable, analogous to homozygous p.Leu710Ser inWDR19 causing either isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B is required for retinal integrity, and we propose POC1B mutations as a probable cause for JBTS with severe polycystic kidney disease.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes