In:
European Journal of Human Genetics, Springer Science and Business Media LLC, Vol. 28, No. 5 ( 2020-05), p. 576-586
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.
Type of Medium:
Online Resource
ISSN:
1018-4813
,
1476-5438
DOI:
10.1038/s41431-019-0548-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2020
detail.hit.zdb_id:
2005160-8
SSG:
12
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