@article {467,
	title = {Re-evaluation casts doubt on the pathogenicity of homozygous USH2A p.C759F.},
	journal = {Am J Med Genet A},
	volume = {167},
	year = {2015},
	month = {2015 Jul},
	pages = {1597-600},
	abstract = {<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>},
	keywords = {Base Sequence, Cyclic Nucleotide Phosphodiesterases, Type 6, Extracellular Matrix Proteins, Gene Library, Humans, Molecular Sequence Data, Mutation, Missense, Pedigree, Retinitis pigmentosa, Sequence Analysis, DNA, Spain},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.37003},
	author = {Pozo, Mar{\'\i}a Gonz{\'a}lez-Del and Bravo-Gil, Nereida and M{\'e}ndez-Vidal, Cristina and Montero-de-Espinosa, Ignacio and Mill{\'a}n, Jos{\'e} M and Dopazo, Joaquin and Borrego, Salud and Anti{\v n}olo, Guillermo}
}
@article {489,
	title = {Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies.},
	journal = {PLoS One},
	volume = {9},
	year = {2014},
	month = {2014},
	pages = {e116176},
	abstract = {<p>This study aimed to identify the underlying molecular genetic cause in four Spanish families clinically diagnosed of Retinitis Pigmentosa (RP), comprising one autosomal dominant RP (adRP), two autosomal recessive RP (arRP) and one with two possible modes of inheritance: arRP or X-Linked RP (XLRP). We performed whole exome sequencing (WES) using NimbleGen SeqCap EZ Exome V3 sample preparation kit and SOLID 5500xl platform. All variants passing filter criteria were validated by Sanger sequencing to confirm familial segregation and the absence in local control population. This strategy allowed the detection of: (i) one novel heterozygous splice-site deletion in RHO, c.937-2_944del, (ii) one rare homozygous mutation in C2orf71, c.1795T>C; p.Cys599Arg, not previously associated with the disease, (iii) two heterozygous null mutations in ABCA4, c.2041C>T; p.R681* and c.6088C>T; p.R2030*, and (iv) one mutation, c.2405-2406delAG; p.Glu802Glyfs*31 in the ORF15 of RPGR. The molecular findings for RHO and C2orf71 confirmed the initial diagnosis of adRP and arRP, respectively, while patients with the two ABCA4 mutations, both previously associated with Stargardt disease, presented symptoms of RP with early macular involvement. Finally, the X-Linked inheritance was confirmed for the family with the RPGR mutation. This latter finding allowed the inclusion of carrier sisters in our preimplantational genetic diagnosis program. </p>},
	keywords = {Adolescent, Adult, Amino Acid Sequence, Base Sequence, Child, Chromosome Segregation, DNA Mutational Analysis, Exome, Family, Female, Humans, Inheritance Patterns, Male, Middle Aged, Molecular Sequence Data, mutation, Pedigree, Retinal Dystrophies, Rhodopsin},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0116176},
	author = {Gonz{\'a}lez-del Pozo, Mar{\'\i}a and M{\'e}ndez-Vidal, Cristina and Bravo-Gil, Nereida and Vela-Boza, Alicia and Dopazo, Joaquin and Borrego, Salud and Anti{\v n}olo, Guillermo}
}
