Abstract
Thirty percent of all inherited retinal disease (IRD) is accounted for by conditions with extra-ocular features. This study aimed to establish the genetic diagnostic pick-up rate for IRD patients with one or more extra-ocular features undergoing panel-based screening in a clinical setting. One hundred and six participants, tested on a gene panel which contained both isolated and syndromic IRD genes, were retrospectively ascertained from the Manchester Genomic Diagnostics Laboratory database spanning 6 years (2012–2017). Phenotypic features were extracted from the clinical notes and classified according to Human Phenotype Ontology; all identified genetic variants were interpreted in accordance to the American College of Medical Genetics and Genomics guidelines. Overall, 49% (
n
= 52) of patients received a probable genetic diagnosis. A further 6% (
n
= 6) had a single disease-associated variant in an autosomal recessive disease-relevant gene. Fifty-two percent (
n
= 55) of patients had a clinical diagnosis at the time of testing. Of these, 71% (
n
= 39) received a probable genetic diagnosis. By contrast, for those without a provisional clinical diagnosis (
n
= 51), only 25% (
n
= 13) received a probable genetic diagnosis. The clinical diagnosis of Usher (
n
= 33) and Bardet–Biedl syndrome (
n
= 10) was confirmed in 67% (
n
= 22) and 80% (
n
= 8), respectively. The testing diagnostic rate in patients with clinically diagnosed multisystemic IRD conditions was significantly higher than those without one (71% versus 25%;
p
value < 0.001). The lower pick-up rate in patients without a clinical diagnosis suggests that panel-based approaches are unlikely to be the most effective means of achieving a molecular diagnosis for this group. Here, we suggest that genome-wide approaches (whole exome or genome) are more appropriate.