By linkage mapping, Bowne et al. (2002) identified 2 American families with the RP10 form of adRP and used these families to reduce the linkage interval to 3.45 Mb between the flanking markers D7S686 and RP-STR8. Ten retinal transcripts ...By linkage mapping, Bowne et al. (2002) identified 2 American families with the RP10 form of adRP and used these families to reduce the linkage interval to 3.45 Mb between the flanking markers D7S686 and RP-STR8. Ten retinal transcripts were identified among 54 independent genes within the candidate region, including the IMP dehydrogenase-1 gene (IMPDH1; 146690). DNA sequencing of affected individuals from 3 RP10 families revealed an asp226-to-asn substitution (146690.0001). Asp226 is highly evolutionarily conserved among IMPDH genes, suggesting that this mutation may be highly deleterious. Another IMPDH1 substitution, val268 to ile (146690.0002), was observed in one of a cohort of 60 adRP families but not in controls. IMPDH1 is a ubiquitously expressed enzyme, functioning as a homotetramer, which catalyzes the rate-limiting step in de novo synthesis of guanine nucleotides. As such, it may play an important role in cyclic nucleotide metabolism within photoreceptors. Kennan et al. (2002) used microarray analysis to compare retinal transcript levels between wildtype mice and those with a targeted disruption of the rhodopsin gene (183830), designated Rho -/-. The gene for IMP dehydrogenase-1 (IMPDH1; 146690) was identified among a series of transcripts present at reduced levels. Mutational screening of DNA from the Spanish adRP family revealed an arg224-to-pro substitution (146690.0003) cosegregating with the disease phenotype. Arg224 of the IMPDH1 protein is conserved among species, and the substitution was not present in a European control population. The authors suggested that additional genes identified in this screen may be prime candidates for etiologic involvement in degenerative retinal disease