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G.H. Mylvaganam, T.L. McGee, E.L. Berson, T.P. Dryja; A Screen for Mutations in the GNB1 Gene in Patients With Autosomal Dominant Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1702.
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© ARVO (1962-2015); The Authors (2016-present)
Transducin is a heterotrimeric G–protein which responds to activated rhodopsin and in consequence activates photophosphodiesterase; it thus serves as the intermediary step in phototransduction. Another group has reported that the autosomal dominant retinal degeneration in the mouse strain Rd4 is associated with an inversion in the gnb1 gene which normally encodes the beta subunit of rod transducin (Kitamura et al. Invest. Ophthalmol. Vis. Sci. 2005 46: E–Abstract 3193). Murine gnb1 consists of 9 coding exons and 3 uncoding exons, and the inversion is found in intron 2 upstream of the initiating methionine codon located in exon 3. The inversion would interrupt the 5' untranslated region and likely create a null gnb1 allele. Gnb1 hemizygosity would result in a reduction of the encoded protein, and the roughly 50% reduction in gnb1 activity could conceivably account for the associated retinal degeneration. If this mechanism is correct, it is possible that humans who are similarly hemizygous for null GNB1 mutations might also develop a dominant retinal degeneration. In this study we searched for such individuals.
We designed PCR conditions to amplify all 12 exons in human GNB1. The DNA fragments amplified from leukocyte DNA from 187 unrelated patients with autosomal dominant retinitis pigmentosa (ADRP) were analyzed by direct sequencing. Many of these patients had been screened for mutations in other dominant RP genes; those with identified mutations were excluded from this study.
We found two polymorphisms in intron 6 (IVS6+19C–T, minor allele frequency = 10%; and IVS6+14G–A, 10%), one polymorphism in intron 4 (IVS4+52C–A, 1%), and a rare variant in intron 5 (IVS5+37C–T, 0.2%). No changes were found in the open reading frame (exons 3–11) or in the noncoding exons 2 and 12. Analysis of exon 1 is still in progress.
No GNB1 mutations have been found in any of 187 unrelated patients with ADRP. This result would be expected if hemizygosity for GNB1 does not result in retinal degeneration in humans.
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