@article {452,
	title = {Improving the management of Inherited Retinal Dystrophies by targeted sequencing of a population-specific gene panel.},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {2016 Apr 01},
	pages = {23910},
	abstract = {<p>Next-generation sequencing (NGS) has overcome important limitations to the molecular diagnosis of Inherited Retinal Dystrophies (IRD) such as the high clinical and genetic heterogeneity and the overlapping phenotypes. The purpose of this study was the identification of the genetic defect in 32 Spanish families with different forms of IRD. With that aim, we implemented a custom NGS panel comprising 64 IRD-associated genes in our population, and three disease-associated intronic regions. A total of 37 pathogenic mutations (14 novels) were found in 73\% of IRD patients ranging from 50\% for autosomal dominant cases, 75\% for syndromic cases, 83\% for autosomal recessive cases, and 100\% for X-linked cases. Additionally, unexpected phenotype-genotype correlations were found in 6 probands, which led to the refinement of their clinical diagnoses. Furthermore, intra- and interfamilial phenotypic variability was observed in two cases. Moreover, two cases unsuccessfully analysed by exome sequencing were resolved by applying this panel. Our results demonstrate that this hypothesis-free approach based on frequently mutated, population-specific loci is highly cost-efficient for the routine diagnosis of this heterogeneous condition and allows the unbiased analysis of a miscellaneous cohort. The molecular information found here has aid clinical diagnosis and has improved genetic counselling and patient management. </p>},
	keywords = {Alleles, Computer Simulation, DNA Copy Number Variations, DNA Mutational Analysis, Eye Proteins, Gene Library, Genetic Association Studies, Genetic Heterogeneity, Genetic Therapy, High-Throughput Nucleotide Sequencing, Humans, mutation, Phenotype, Retinal Dystrophies},
	issn = {2045-2322},
	doi = {10.1038/srep23910},
	author = {Bravo-Gil, Nereida and M{\'e}ndez-Vidal, Cristina and Romero-P{\'e}rez, Laura and Gonz{\'a}lez-del Pozo, Mar{\'\i}a and Rodr{\'\i}guez-de la R{\'u}a, Enrique and Dopazo, Joaquin and Borrego, Salud and Anti{\v n}olo, Guillermo}
}
@article {536,
	title = {Mutation screening of multiple genes in Spanish patients with autosomal recessive retinitis pigmentosa by targeted resequencing.},
	journal = {PLoS One},
	volume = {6},
	year = {2011},
	month = {2011},
	pages = {e27894},
	abstract = {<p>Retinitis Pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. RP is the leading cause of visual loss in individuals younger than 60 years, with a prevalence of about 1 in 4000. The molecular genetic diagnosis of autosomal recessive RP (arRP) is challenging due to the large genetic and clinical heterogeneity. Traditional methods for sequencing arRP genes are often laborious and not easily available and a screening technique that enables the rapid detection of the genetic cause would be very helpful in the clinical practice. The goal of this study was to develop and apply microarray-based resequencing technology capable of detecting both known and novel mutations on a single high-throughput platform. Hence, the coding regions and exon/intron boundaries of 16 arRP genes were resequenced using microarrays in 102 Spanish patients with clinical diagnosis of arRP. All the detected variations were confirmed by direct sequencing and potential pathogenicity was assessed by functional predictions and frequency in controls. For validation purposes 4 positive controls for variants consisting of previously identified changes were hybridized on the array. As a result of the screening, we detected 44 variants, of which 15 are very likely pathogenic detected in 14 arRP families (14\%). Finally, the design of this array can easily be transformed in an equivalent diagnostic system based on targeted enrichment followed by next generation sequencing.</p>},
	keywords = {Alleles, DNA Mutational Analysis, Exons, Genetic Variation, Genome, Hispanic or Latino, Humans, Introns, Language, mutation, Mutation, Missense, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Reproducibility of Results, Retinitis pigmentosa, United States},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0027894},
	author = {Gonz{\'a}lez-del Pozo, Mar{\'\i}a and Borrego, Salud and Barrag{\'a}n, Isabel and Pieras, Juan I and Santoyo, Javier and Matamala, Nerea and Naranjo, Bel{\'e}n and Dopazo, Joaquin and Anti{\v n}olo, Guillermo}
}
