Recessive mutations in the gene encoding the β–subunit of rod phosphodiesterase in patients with retinitis pigmentosa

Abstract

We have found four mutations in the human gene encoding the beta-subunit of rod cGMP phosphodiesterase (PDE beta) that cosegregate with autosomal recessive retinitis pigmentosa, a degenerative disease of photoreceptors. In one family two affected siblings both carry allelic nonsense mutations at codons 298 and 531. Affected individuals have abnormal rod and cone electroretinograms. PDE beta is the second member of the phototransduction cascade besides rhodopsin that is absent or altered as a cause of retinitis pigmentosa, suggesting that other members of this pathway may be defective in other forms of this disease.

An Arabidopsis Mutant Hypersensitive to Red and Far-Red Light Signals

“…In Drosophila, the absence of arrestin, a protein that negatively regulates photoreceptor activity, could induce a light-dependent retinal degeneration (Dolph et al, 1993). In human retinitis pigmentosa diseases, deregulation of rhodopsin signaling leading to an accumulation of signal intermediates (e.g., cGMP) can cause cell degeneration and induce programmed cell death (Farrar et al, 1991;McLaughlin et al, 1993;Dryja et al, 1995). Similar mechanisms may apply here.…”

Gene supplementation therapy for recessive forms of inherited retinal dystrophies

“…61 This approach results in rescue of the ERG to 37 % of wild type, which was threefold higher than in untreated eyes, and preservation of 60% of photoreceptor cells when only a few cells survive in untreated eyes. As the rate of retinal degeneration in humans with RP40 (b-PDE deficiency) is more comparable to that in the Rd10 mouse than the Rd1-null mutant, 62 the results of the Rd10 study suggest that the disease in humans might be more amenable to treatment than the earlier results of experiments in Rd1 mice had indicated. LCA type 4, or AIPL1 deficiency, is a disorder closely related to b-PDE deficiency.…”

The molecular basis of human retinal and vitreoretinal diseases

“…Therefore, a differential diagnosis by genetic testing can provide helpful and important information to the affected individuals and families, in order to exclude or confirm the clinical diagnosis and to provide counselling. Bech-Hansen et al, 1998; Bech-Hansen et al, 2000;Dryja et al, 1993; Dryja et al, 1996; Dryja et al, 2005; Fuchs et al, 1995;Gal et al, 1994;Li et al, 2009; Pusch et al, 2000;Strom et al, 1998;Wycisk et al, 2006;Yamamoto et al, 1997;Zeitz et al, 2005;Zeitz et al, 2006 inheritance. The disease was found to be due to mutations in the alpha subunit of transducin (Dryja et al, 1996).…”

“…The disease onset and progression may vary significantly among patients, even within the same family. The patients frequently experience night blindness in the early phase of the disease, The molecular basis of human retinal and vitreoretinal diseases Collin et al, 2008; den Hollander et al, 1999; Dryja et al, 1995; Gal et al., 2000; Huang et al, 1995; Martinez-Mir et al, 1998;Maw et al, 1997;Maw et al, 2000;McLaughlin et al, 1993; Morimura et al, 1998;Nakazawa et al, 1998; Rivolta et al, 2000;Thompson et al, 2001;Tuson et al, 2004;Zangerl et al, 2006;Zhang et al, 2007b) or dominant (Abid et al, 2006; Bowne et al, 2002; Chakarova et al, 2002; Chakarova et al, 2007;Farrar et al, 1991;Freund et al, 1997;Friedman et al, 2009; Kajiwara et al, 1991; Kajiwara et al, 1994; Keen et al, 2002; Kennan et al, 2002;McKie et al, 2001; Rebello et al, 2004; Sato et al, 2005;Vithana et al, 2001;Wada et al, 2001;Zhang et al, 2007a;Zhao et al, 2009), as well as X-linked (Meindl et al, 1996; Roepman et al, 1996a; Roepman et al, 1996b; Schwahn et al, 1998).Interestingly, mutations in several genes can be either dominant or recessive (Bernal et al, 2008; Bessant et al, 1999; Coppieters et al, 2007;Davidson et al, 2009; Dryja et al, 1990; Morimura et al, 1999; Pierce et al, 1999;Sullivan et al, 1999). The splicing category will now be discussed in more detail.…”