02531nas a2200361   4500008004100000022001400041245008000055210006900135260001300204300001300217490000800230520137100238653001801609653004901627653003401676653001701710653001101727653002801738653002301766653001301789653002501802653002701827653001001854100003301864700002301897700002801920700003301948700002201981700002002003700001902023700002502042856010202067       2015                        eng d  a1552-483300aRe-evaluation casts doubt on the pathogenicity of homozygous USH2A p.C759F.0 aReevaluation casts doubt on the pathogenicity of homozygous USH2  c2015 Jul  a1597-6000 v1673 a<p>Mutations in USH2A are a common cause of Retinitis Pigmentosa (RP). Among the most frequently reported USH2A variants, c.2276G>T (p.C759F) has been found in both affected and healthy individuals. The pathogenicity of this variant remains controversial since it was detected in homozygosity in two healthy siblings of a Spanish family (S23), eleven years ago. The fact that these individuals remain asymptomatic today, prompted us to study the presence of other pathogenic variants in this family using targeted resequencing of 26 retinal genes in one of the affected individuals. This approach allowed us to identify one novel pathogenic homozygous mutation in exon 13 of PDE6B (c.1678C>T; p.R560C). This variant cosegregated with the disease and was absent in 200 control individuals. Remarkably, the identified variant in PDE6B corresponds to the mutation responsible of the retinal degeneration in the naturally occurring rd10 mutant mice. To our knowledge, this is the first report of the identification of the rd10 mice mutation in a RP family. These findings, together with a review of the literature, support the hypothesis that homozygous p.C759F mutations are not pathogenic and led us to exclude the implication of p.C759F in the RP of family S23. Our results indicate the need of re-evaluating all families genetically diagnosed with this mutation.</p>10aBase Sequence10aCyclic Nucleotide Phosphodiesterases, Type 610aExtracellular Matrix Proteins10aGene Library10aHumans10aMolecular Sequence Data10aMutation, Missense10aPedigree10aRetinitis pigmentosa10aSequence Analysis, DNA10aSpain1 aDel Pozo, María, González-1 aBravo-Gil, Nereida1 aMéndez-Vidal, Cristina1 aMontero-de-Espinosa, Ignacio1 aMillán, José, M1 aDopazo, Joaquin1 aBorrego, Salud1 aAntiňolo, Guillermo  uhttp://clinbioinfosspa.es/content/re-evaluation-casts-doubt-pathogenicity-homozygous-ush2a-pc759f