PUBLICATION
Disruption of the Basal Body Protein POC1B Results in Autosomal-Recessive Cone-Rod Dystrophy
- Authors
- Roosing, S., Lamers, I.J., de Vrieze, E., van den Born, L.I., Lambertus, S., Arts, H.H., POC1B Study Group, Peters, T.A., Hoyng, C.B., Kremer, H., Hetterschijt, L., Letteboer, S.J., van Wijk, E., Roepman, R., den Hollander, A.I., Cremers, F.P.
- ID
- ZDB-PUB-140716-16
- Date
- 2014
- Source
- American journal of human genetics 95(2): 131-142 (Journal)
- Registered Authors
- de Vrieze, Erik, Hetterschijt, Lisette, Kremer, Hannie, van Wijk, Erwin
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Basal Bodies
- Base Sequence
- Cell Cycle Proteins/genetics*
- Cell Cycle Proteins/metabolism
- Cells, Cultured
- Exome/genetics
- Eye Proteins/genetics
- Eye Proteins/metabolism*
- 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 Pigment Epithelium/pathology
- Retinal Rod Photoreceptor Cells/pathology*
- Retinitis Pigmentosa/genetics*
- Sequence Analysis, DNA
- Turkey
- Vision Disorders/genetics
- Zebrafish
- PubMed
- 25018096 Full text @ Am. J. Hum. Genet.
Citation
Roosing, S., Lamers, I.J., de Vrieze, E., van den Born, L.I., Lambertus, S., Arts, H.H., POC1B Study Group, Peters, T.A., Hoyng, C.B., Kremer, H., Hetterschijt, L., Letteboer, S.J., van Wijk, E., Roepman, R., den Hollander, A.I., Cremers, F.P. (2014) Disruption of the Basal Body Protein POC1B Results in Autosomal-Recessive Cone-Rod Dystrophy. American journal of human genetics. 95(2):131-142.
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.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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping