The Genetic Basis of IRDS and the Role of Genetic Testing

Most of the major clinical IRD) phenotypes are monogenic conditions and demonstrate classic Mendelian inheritance patterns. More than 300 genes have been implicated in IRDs, many of which are involved in phototransduction, the retinoid cycle, photoreceptor cell structure, structure and function of the connecting cilium, transcription factors, and RNA splicing (Fig. 58.1; Hamel 2014; Dias et al. 2018). Studies involving relatively large patient cohorts have documented 4798 discrete variants in 194 genes (Schneider et al. 2022). The majority of variants either alter one or more amino acid in sequence (missense mutations) or prematurely truncate proteins (nonsense mutations). Smaller percentages of mutations affect RNA splicing, start and stop codons, or control regions (Schneider et al. 2022).