3.1.1. Prph2R172W

One of the most common disease-causing mutations of *PRPH2* is the substitution of tryptophan to arginine at position 172 (R172W) [96–99]. Patients carrying this mutation display a decrease in cone function, while rods' function remains unaffected [96]. The R172W mutation is located in the D2 loop, which is the region that promotes complex formation and where the vast majority of pathogenic *PRPH2* mutations are located [22,87]. Interestingly, the R172W mutation is located outside the part of the D2 loop involved in the formation of complexes [22]. Expressing the R172W mutation in the presence of the full complement of WT Prph2 led initially to normal rod function and structure [87]. In contrast, the retina of these mice exhibited a significant loss in the number of blue and green cones and associated with a decrease in their photopic responses. When expressed on *Prph2*+/− background, the R172W mutation led to a late-onset reduction in the number of rod cells and in scotopic responses, besides the cone phenotype. This varies from the cone exclusive phenotype observed in patients carrying this mutation and is most likely due to haploinsufficiency of Prph2. Expression of the R172W mutation in the *Nrl*−/− retina reproduced the functional decline in the photopic responses and provided evidence as to how the R172W mutation disrupted COS structures by causing the formation of abnormal high molecular weight Prph2/Rom1 aggregates [81]. This result demonstrates how the functional decline of the cones occurs in patients carrying this mutation.
