Whole-exome sequencing reveals POC5 as a novel gene associated with autosomal recessive retinitis pigmentosa
- Weisz Hubshman, M., Broekman, S., van Wijk, E., Cremers, F., Abu-Diab, A., Samer, K., Tzur, S., Lagovsky, I., Smirin-Yosef, P., Sharon, D., Haer-Wigman, L., Banin, E., Basel-Vanagaite, L., de Vrieze, E.
- Human molecular genetics 27(4): 614-624 (Journal)
- Registered Authors
- de Vrieze, Erik, van Wijk, Erwin
- MeSH Terms
- Carrier Proteins/genetics*
- Retinitis Pigmentosa/genetics*
- Young Adult
- 29272404 Full text @ Hum. Mol. Genet.
Weisz Hubshman, M., Broekman, S., van Wijk, E., Cremers, F., Abu-Diab, A., Samer, K., Tzur, S., Lagovsky, I., Smirin-Yosef, P., Sharon, D., Haer-Wigman, L., Banin, E., Basel-Vanagaite, L., de Vrieze, E. (2017) Whole-exome sequencing reveals POC5 as a novel gene associated with autosomal recessive retinitis pigmentosa. Human molecular genetics. 27(4):614-624.
Retinitis pigmentosa (RP), the most common form of inherited retinal degeneration, is associated with different groups of genes, including those encoding proteins involved in centriole and cilium biogenesis. Exome sequencing revealed a homozygous nonsense mutation (c.304_305delGA [p. D102*]) in POC5, encoding the Proteome Of Centriole 5, in a patient with retinitis pigmentosa, short stature, microcephaly and recurrent glomerulonephritis. The POC5 gene is ubiquitously expressed, and immunohistochemistry revealed a distinct POC5 localization at the photoreceptor connecting cilium. Morpholino-oligonucleotide-induced knockdown of poc5 translation in zebrafish resulted in decreased length of photoreceptor outer segments and a decreased visual motor response (VMR), a measurement of retinal function. These phenotypes could be rescued by wild-type human POC5 mRNA. These findings demonstrate that Poc5 is important for normal retinal development and function. Altogether, this study presents POC5 as a novel gene involved autosomal recessively inherited retinitis pigmentosa, and strengthens the hypothesis that mutations in centriolar proteins are important cause of retinal dystrophies.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes