02872nas a2200373   4500008004100000022001400041245013900055210006900194260001600263300001400279490000700293520162700300100003001927700002401957700001801981700003201999700002002031700001802051700002802069700002202097700003402119700002602153700003302179700002802212700002702240700001802267700002902285700002002314700002802334700001902362700002002381700001802401856007902419       2015                        eng d  a1460-208300aWhole Exome Sequencing Reveals ZNF408 as a New Gene Associated With Autosomal Recessive Retinitis Pigmentosa with Vitreal Alterations.0 aWhole Exome Sequencing Reveals ZNF408 as a New Gene Associated W  c2015 Apr 16  a4037-40480 v243 aRetinitis 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 ten 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.1 aAvila-Fernandez, Almudena1 aPerez-Carro, Raquel1 aCorton, Marta1 aLopez-Molina, Maria, Isabel1 aCampello, Laura1 aGaranto, Alex1 aFernadez-Sanchez, Laura1 aDuijkers, Lonneke1 aLopez-Martinez, Miguel, Angel1 aRiveiro-Alvarez, Rosa1 ada Silva, Luciana, Rodrigues1 aSanchez-Alcudia, Rocío1 aMartin-Garrido, Esther1 aReyes, Noelia1 aGarcia-Garcia, Francisco1 aDopazo, Joaquin1 aGarcia-Sandoval, Blanca1 aCollin, Rob, W1 aCuenca, Nicolas1 aAyuso, Carmen  uhttp://hmg.oxfordjournals.org/content/early/2015/04/16/hmg.ddv140.abstract03593nas a2200601   4500008004100000022001400041245013900055210006900194260001600263300001200279490000700291520163400298653002401932653001201956653002501968653002301993653001402016653002502030653001002055653003402065653004202099653001502141653001102156653002802167653002002195653001302215653001102228653003702239653003602276653002502312653002602337100003002363700002402393700001802417700003202435700002002467700002302487700002902510700002202539700003402561700002602595700003302621700002802654700002702682700001802709700002902727700002002756700002802776700002102804700002002825700001802845856012802863       2015                        eng d  a1460-208300aWhole-exome sequencing reveals ZNF408 as a new gene associated with autosomal recessive retinitis pigmentosa with vitreal alterations.0 aWholeexome sequencing reveals ZNF408 as a new gene associated wi  c2015 Jul 15  a4037-480 v243 a<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>10aAmino Acid Sequence10aAnimals10aChlorocebus aethiops10aChromosome Mapping10aCOS Cells10aDNA-Binding Proteins10aExome10aGenome-Wide Association Study10aHigh-Throughput Nucleotide Sequencing10aHomozygote10aHumans10aMolecular Sequence Data10aMutant Proteins10aPedigree10aRetina10aRetinal Cone Photoreceptor Cells10aRetinal Rod Photoreceptor Cells10aRetinitis pigmentosa10aTranscription Factors1 aAvila-Fernandez, Almudena1 aPerez-Carro, Raquel1 aCorton, Marta1 aLopez-Molina, Maria, Isabel1 aCampello, Laura1 aGaranto, Alejandro1 aFernandez-Sanchez, Laura1 aDuijkers, Lonneke1 aLopez-Martinez, Miguel, Angel1 aRiveiro-Alvarez, Rosa1 ada Silva, Luciana, Rodrigues1 aSanchez-Alcudia, Rocío1 aMartin-Garrido, Esther1 aReyes, Noelia1 aGarcia-Garcia, Francisco1 aDopazo, Joaquin1 aGarcia-Sandoval, Blanca1 aCollin, Rob, W J1 aCuenca, Nicolas1 aAyuso, Carmen  uhttp://clinbioinfosspa.es/content/whole-exome-sequencing-reveals-znf408-new-gene-associated-autosomal-recessive-retinitis-0