02776nas a2200445 4500008004100000022001400041245012000055210006900175260000900244300001200253490000600265520144600271653001501717653001001732653002401742653001801766653001001784653002701794653002801821653001001849653001101859653001101870653001101881653002501892653000901917653001601926653002801942653001301970653001301983653002401996653001402020100003302034700002802067700002302095700002202118700002002140700001902160700002502179856012602204 2014 eng d a1932-620300aExome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies.0 aExome sequencing reveals novel and recurrent mutations with clin c2014 ae1161760 v93 a
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.
10aAdolescent10aAdult10aAmino Acid Sequence10aBase Sequence10aChild10aChromosome Segregation10aDNA Mutational Analysis10aExome10aFamily10aFemale10aHumans10aInheritance Patterns10aMale10aMiddle Aged10aMolecular Sequence Data10amutation10aPedigree10aRetinal Dystrophies10aRhodopsin1 adel Pozo, María, González-1 aMéndez-Vidal, Cristina1 aBravo-Gil, Nereida1 aVela-Boza, Alicia1 aDopazo, Joaquin1 aBorrego, Salud1 aAntiňolo, Guillermo uhttps://clinbioinfosspa.es/content/exome-sequencing-reveals-novel-and-recurrent-mutations-clinical-significance-inherited