Re-evaluation casts doubt on the pathogenicity of homozygous XXXX @entity24130 .

@entity24130 @entity2000 @entity71321 @entity19 @entity6391 @entity71320 @entity28614 @entity71319 @entity27763
UNASSIGNED: Mutations in @entity28614 are a common cause of @entity6391 ( @entity6391 ). Among the most frequently reported @entity28614 variants, @entity71319 ( @entity24130 ) 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 @entity27763 ( @entity71320 ; @entity71321 ). This variant cosegregated with the disease and was absent in 200 control individuals. Remarkably, the identified variant in @entity27763 corresponds to the mutation responsible of the @entity2000 in the naturally occurring @entity27763 mutant @entity19 . To our knowledge, this is the first report of the identification of the @entity27763 @entity19 mutation in a @entity6391 family. These findings, together with a review of the literature, support the hypothesis that homozygous @entity24130 mutations are not pathogenic and led us to exclude the implication of @entity24130 in the @entity6391 of family S23. Our results indicate the need of re-evaluating all families genetically diagnosed with this mutation.    2015 Wiley Periodicals, Inc.
