TY - JOUR T1 - In vitro analysis of aminoglycoside therapy for the Arg120stop nonsense mutation in RP2 patients JF - Journal of Medical Genetics JO - J Med Genet SP - 62 LP - 67 DO - 10.1136/jmg.39.1.62 VL - 39 IS - 1 AU - C Grayson AU - J P Chapple AU - K R Willison AU - A R Webster AU - A J Hardcastle AU - M E Cheetham Y1 - 2002/01/01 UR - http://jmg.bmj.com/content/39/1/62.abstract N2 - X linked retinitis pigmentosa (XLRP) is a heterogeneous disease causing a severe form of retinal degeneration. Patients typically present with night blindness and constricted visual fields within the first two decades of life owing to peripheral photoreceptor degeneration. As the disease progresses, impairment of central vision occurs resulting in loss of visual acuity and complete functional blindness often by the age of 40-50 years.1 The gene that causes one form of this disease, RP2, has recently been positionally cloned and has been shown to account for between 15-20% of XLRP.2 The RP2 gene consists of five exons encoding a polypeptide of 350 amino acids and is ubiquitously expressed. There are currently few functional data available about this protein. One functional clue is a similarity to cofactor C with the predicted RP2 amino acid sequence having 30.4% identity over 151 amino acids.2 Cofactor C was initially thought to play a role in the folding of β-tubulin,3,4 suggesting that RP2 could also be involved in tubulin biogenesis. A recent study has shown, however, that RP2 undergoes N-terminal acyl modification and thus has a predominantly plasma membrane localisation in cultured cells.5 For this reason it seems unlikely that RP2 functions exclusively in tubulin folding and its precise function and any specific role in the retina are at present unknown. Mutation screening in XLRP patients has identified over 20 different pathogenic mutations in the RP2 gene, including missense, frameshift, insertion, and deletion changes.2,6–11 There are also three different identified nonsense mutations causing a premature stop within the first two exons of the gene.2,6–8In this study, we have investigated a potential drug mediated therapy to restore RP2 function in patients with nonsense mutations, in particular the opal nonsense mutation converting CGA … ER -