Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy

Susanne Roosing, Ideke J C Lamers, Erik de Vrieze, L Ingeborgh van den Born, Stanley Lambertus, Heleen H Arts, , Theo A Peters, Carel B Hoyng, Hannie Kremer, Lisette Hetterschijt, Stef J F Letteboer, Erwin van Wijk, Ronald Roepman, Anneke I den Hollander, Frans P M Cremers

Research output: Contribution to journalArticleResearchpeer-review


Exome sequencing revealed a homozygous missense mutation (c.317C>G [p.Arg106Pro]) in POC1B, encoding POC1 centriolar protein B, in three siblings with autosomal-recessive cone dystrophy or cone-rod dystrophy and compound-heterozygous POC1B mutations (c.199_201del [p.Gln67del] and c.810+1G>T) in an unrelated person with cone-rod dystrophy. Upon overexpression of POC1B in human TERT-immortalized retinal pigment epithelium 1 cells, the encoded wild-type protein localized to the basal body of the primary cilium, whereas this localization was lost for p.Arg106Pro and p.Gln67del variant forms of POC1B. Morpholino-oligonucleotide-induced knockdown of poc1b translation in zebrafish resulted in a dose-dependent small-eye phenotype, impaired optokinetic responses, and decreased length of photoreceptor outer segments. These ocular phenotypes could partially be rescued by wild-type human POC1B mRNA, but not by c.199_201del and c.317C>G mutant human POC1B mRNAs. Yeast two-hybrid screening of a human retinal cDNA library revealed FAM161A as a binary interaction partner of POC1B. This was confirmed in coimmunoprecipitation and colocalization assays, which both showed loss of FAM161A interaction with p.Arg106Pro and p.Gln67del variant forms of POC1B. FAM161A was previously implicated in autosomal-recessive retinitis pigmentosa and shown to be located at the base of the photoreceptor connecting cilium, where it interacts with several other ciliopathy-associated proteins. Altogether, this study demonstrates that POC1B mutations result in a defect of the photoreceptor sensory cilium and thus affect cone and rod photoreceptors.

Original languageEnglish
Pages (from-to)131-42
Number of pages12
JournalAmerican Journal of Human Genetics
Issue number2
Publication statusPublished - 7 Aug 2014


  • Amino Acid Sequence
  • Animals
  • Basal Bodies
  • Base Sequence
  • Cell Cycle Proteins/genetics
  • Cells, Cultured
  • Exome/genetics
  • Eye Proteins/genetics
  • Female
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Male
  • Molecular Sequence Data
  • Morpholinos/genetics
  • Mutation, Missense
  • Netherlands
  • Photoreceptor Connecting Cilium/metabolism
  • Retinal Cone Photoreceptor Cells/pathology
  • Retinal Photoreceptor Cell Outer Segment/physiology
  • Retinal Pigment Epithelium/metabolism
  • Retinal Rod Photoreceptor Cells/pathology
  • Retinitis Pigmentosa/genetics
  • Sequence Analysis, DNA
  • Turkey
  • Vision Disorders/genetics
  • Zebrafish


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