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

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Abstract
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.G1n67del] 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.G1n67del 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.G1n67del 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.
Keywords
JOUBERT-SYNDROME, CENTROSOMAL PROTEIN, RETINITIS-PIGMENTOSA, LEBER CONGENITAL AMAUROSIS, CENTRIOLE DUPLICATION, RETINAL DYSTROPHIES, GENE-THERAPY, MUTATIONS, CILIARY PROTEIN, ACHROMATOPSIA

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MLA
Roosing, Susanne, et al. “Disruption of the Basal Body Protein POC1B Results in Autosomal-Recessive Cone-Rod Dystrophy.” AMERICAN JOURNAL OF HUMAN GENETICS, vol. 95, no. 2, 2014, pp. 131–42, doi:10.1016/j.ajhg.2014.06.012.
APA
Roosing, S., Lamers, I. J., de Vrieze, E., van den Born, L. I., Lambertus, S., Arts, H. H., … POC1B Study Group, the. (2014). Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy. AMERICAN JOURNAL OF HUMAN GENETICS, 95(2), 131–142. https://doi.org/10.1016/j.ajhg.2014.06.012
Chicago author-date
Roosing, Susanne, Ideke JC Lamers, Erik de Vrieze, L Ingeborgh van den Born, Stanley Lambertus, Heleen H Arts, Theo A Peters, et al. 2014. “Disruption of the Basal Body Protein POC1B Results in Autosomal-Recessive Cone-Rod Dystrophy.” AMERICAN JOURNAL OF HUMAN GENETICS 95 (2): 131–42. https://doi.org/10.1016/j.ajhg.2014.06.012.
Chicago author-date (all authors)
Roosing, Susanne, Ideke JC 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 JF Letteboer, Erwin van Wijk, Ronald Roepman, Anneke I den Hollander, Frans PM Cremers, Frauke Coppieters, Elfride De Baere, and the POC1B Study Group. 2014. “Disruption of the Basal Body Protein POC1B Results in Autosomal-Recessive Cone-Rod Dystrophy.” AMERICAN JOURNAL OF HUMAN GENETICS 95 (2): 131–142. doi:10.1016/j.ajhg.2014.06.012.
Vancouver
1.
Roosing S, Lamers IJ, de Vrieze E, van den Born LI, Lambertus S, Arts HH, et al. Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy. AMERICAN JOURNAL OF HUMAN GENETICS. 2014;95(2):131–42.
IEEE
[1]
S. Roosing et al., “Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy,” AMERICAN JOURNAL OF HUMAN GENETICS, vol. 95, no. 2, pp. 131–142, 2014.
@article{5847131,
  abstract     = {{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.G1n67del] 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.G1n67del 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.G1n67del 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.}},
  author       = {{Roosing, Susanne and Lamers, Ideke JC and de Vrieze, Erik and van den Born, L Ingeborgh and Lambertus, Stanley and Arts, Heleen H and Peters, Theo A and Hoyng, Carel B and Kremer, Hannie and Hetterschijt, Lisette and Letteboer, Stef JF and van Wijk, Erwin and Roepman, Ronald and den Hollander, Anneke I and Cremers, Frans PM and Coppieters, Frauke and De Baere, Elfride and POC1B Study Group, the}},
  issn         = {{0002-9297}},
  journal      = {{AMERICAN JOURNAL OF HUMAN GENETICS}},
  keywords     = {{JOUBERT-SYNDROME,CENTROSOMAL PROTEIN,RETINITIS-PIGMENTOSA,LEBER CONGENITAL AMAUROSIS,CENTRIOLE DUPLICATION,RETINAL DYSTROPHIES,GENE-THERAPY,MUTATIONS,CILIARY PROTEIN,ACHROMATOPSIA}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{131--142}},
  title        = {{Disruption of the basal body protein POC1B results in autosomal-recessive cone-rod dystrophy}},
  url          = {{http://dx.doi.org/10.1016/j.ajhg.2014.06.012}},
  volume       = {{95}},
  year         = {{2014}},
}

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