@article {463,
	title = {Whole-exome sequencing reveals ZNF408 as a new gene associated with autosomal recessive retinitis pigmentosa with vitreal alterations.},
	journal = {Hum Mol Genet},
	volume = {24},
	year = {2015},
	month = {2015 Jul 15},
	pages = {4037-48},
	abstract = {<p>Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies that cause visual impairment as a result of photoreceptor cell death. RP is heterogeneous, both clinically and genetically making difficult to establish precise genotype-phenotype correlations. In a Spanish family with autosomal recessive RP (arRP), homozygosity mapping and whole-exome sequencing led to the identification of a homozygous mutation (c.358_359delGT; p.Ala122Leufs*2) in the ZNF408 gene. A screening performed in 217 additional unrelated families revealed another homozygous mutation (c.1621C>T; p.Arg541Cys) in an isolated RP case. ZNF408 encodes a transcription factor that harbors 10 predicted C2H2-type fingers thought to be implicated in DNA binding. To elucidate the ZNF408 role in the retina and the pathogenesis of these mutations we have performed different functional studies. By immunohistochemical analysis in healthy human retina, we identified that ZNF408 is expressed in both cone and rod photoreceptors, in a specific type of amacrine and ganglion cells, and in retinal blood vessels. ZNF408 revealed a cytoplasmic localization and a nuclear distribution in areas corresponding with the euchromatin fraction. Immunolocalization studies showed a partial mislocalization of the p.Arg541Cys mutant protein retaining part of the WT protein in the cytoplasm. Our study demonstrates that ZNF408, previously associated with Familial Exudative Vitreoretinopathy (FEVR), is a new gene causing arRP with vitreous condensations supporting the evidence that this protein plays additional functions into the human retina. </p>},
	keywords = {Amino Acid Sequence, Animals, Chlorocebus aethiops, Chromosome Mapping, COS Cells, DNA-Binding Proteins, Exome, Genome-Wide Association Study, High-Throughput Nucleotide Sequencing, Homozygote, Humans, Molecular Sequence Data, Mutant Proteins, Pedigree, Retina, Retinal Cone Photoreceptor Cells, Retinal Rod Photoreceptor Cells, Retinitis pigmentosa, Transcription Factors},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddv140},
	author = {Avila-Fernandez, Almudena and Perez-Carro, Raquel and Corton, Marta and Lopez-Molina, Maria Isabel and Campello, Laura and Garanto, Alejandro and Fernandez-Sanchez, Laura and Duijkers, Lonneke and Lopez-Martinez, Miguel Angel and Riveiro-Alvarez, Rosa and da Silva, Luciana Rodrigues Jacy and Sanchez-Alcudia, Roc{\'\i}o and Martin-Garrido, Esther and Reyes, Noelia and Garcia-Garcia, Francisco and Dopazo, Joaquin and Garcia-Sandoval, Blanca and Collin, Rob W J and Cuenca, Nicolas and Ayuso, Carmen}
}
