*5.4. NPHP4*

Wire-haired dachshunds have a cone–rod dystrophy resulting from a truncating mutation in *Nphp4*. The identified *Nphp4* mutation was a deletion involving exon 5/intron 5 that led to skipping of exon 5 and a premature truncation in exon 6 of 30 (c.462\_526del, p.Leu155LysfsTer2) [100]. A colony was established from a single founder male [101]. Puppies had miotic pupils and cone-mediated ERGs were reduced prior to retinal maturation. Furthermore, they did not show the normal increase in amplitudes with retinal maturation and further declined in amplitude rapidly. The amplitudes of the rod-driven responses were less severely a ffected, but were lost with age [102,103]. Interestingly, the condition is non-syndromic in dogs, just presenting as a cone–rod dystrophy. Human patients with *NPHP4* mutations do not always develop a retinal phenotype, but typically have nephronophthisis, with some patients having Senior–Løken syndrome, which combines the renal phenotype with a retinal dystrophy (see for [104] a review). This phenotype di fference may represent a species di fference, with *Nphp4*−/− mice also only having an ocular phenotype with no renal abnormalities, but also showing male infertility [105].
