TY - JOUR T1 - Mutation screening of multiple genes in Spanish patients with autosomal recessive retinitis pigmentosa by targeted resequencing. JF - PLoS One Y1 - 2011 A1 - González-del Pozo, María A1 - Borrego, Salud A1 - Barragán, Isabel A1 - Pieras, Juan I A1 - Santoyo, Javier A1 - Matamala, Nerea A1 - Naranjo, Belén A1 - Dopazo, Joaquin A1 - Antiňolo, Guillermo KW - Alleles KW - DNA Mutational Analysis KW - Exons KW - Genetic Variation KW - Genome KW - Hispanic or Latino KW - Humans KW - Introns KW - Language KW - mutation KW - Mutation, Missense KW - Oligonucleotide Array Sequence Analysis KW - Polymerase Chain Reaction KW - Reproducibility of Results KW - Retinitis pigmentosa KW - United States AB -

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.

VL - 6 IS - 12 U1 - https://www.ncbi.nlm.nih.gov/pubmed/22164218?dopt=Abstract ER -