Among 3 families with autosomal dominant retinitis pigmentosa linked to 7q (RP10; 180105), Bowne et al. (2002) identified a G-to-A transition at codon 226 of the IMPDH1 gene, substituting an asparagine for an aspartic acid (D226N). Asp226 is highly evolutionarily conserved among IMPDH genes, suggesting that this mutation may be highly deleterious.
Wada et al. (2005) identified the D226N mutation in 6 of 183 unrelated patients with autosomal dominant RP. Taking into account the 135 patients excluded from the study because of previously identified mutations in other dominant RP genes, Wada et al. (2005) estimated that IMPDH1 mutations account for approximately 2% of cases of dominant RP in North America. Based on a comparison of electroretinogram (ERG) amplitudes among carriers of the IMPDH1 D226N mutation, the RP1 mutation R677X (603937.0001), the rhodopsin mutation P23H (180380.0001), and the rhodopsin mutation P347L (180380.0002), Wada et al. (2005) concluded that D226N, the most frequent mutation, appeared to cause at least as much loss of rod function as cone function, and that patients with this form of RP retained, on average, 2 to 5 times more ERG amplitude per unit of remaining visual area than patients with the 3 other forms of dominant RP.
Bischof et al. (2006) identified a processed pseudogene for IMPDH1 carrying the 676G-A transition that produces the D226N substitution. The authors suggested that this case may represent a novel gene conversion event involving a processed pseudogene.
