RT Journal Article
SR Electronic
T1 Likely pathogenic structural variants in genetically unsolved patients with retinitis pigmentosa revealed by long-read sequencing
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP jmedgenet-2022-108428
DO 10.1136/jmedgenet-2022-108428
A1 Yusuke Sano
A1 Yoshito Koyanagi
A1 Jing Hao Wong
A1 Yusuke Murakami
A1 Kohta Fujiwara
A1 Mikiko Endo
A1 Tomomi Aoi
A1 Kazuki Hashimoto
A1 Toru Nakazawa
A1 Yuko Wada
A1 Shinji Ueno
A1 Dan Gao
A1 Akira Murakami
A1 Yoshihiro Hotta
A1 Yasuhiro Ikeda
A1 Koji M Nishiguchi
A1 Yukihide Momozawa
A1 Koh-Hei Sonoda
A1 Masato Akiyama
A1 Akihiro Fujimoto
YR 2022
UL http://jmg.bmj.com/content/early/2022/06/09/jmedgenet-2022-108428.abstract
AB Despite the successful identification of causative genes and genetic variants of retinitis pigmentosa (RP), many patients have not been molecularly diagnosed. Our recent study using targeted short-read sequencing showed that the proportion of carriers of pathogenic variants in EYS, the cause of autosomal recessive RP, was unexpectedly high in Japanese patients with unsolved RP. This result suggested that causative genetic variants, which are difficult to detect by short-read sequencing, exist in such patients. Using long-read sequencing technology (Oxford Nanopore), we analysed the whole genomes of 15 patients with RP with one heterozygous pathogenic variant in EYS detected in our previous study along with structural variants (SVs) in EYS and another 88 RP-associated genes. Two large exon-overlapping deletions involving six exons were identified in EYS in two patients with unsolved RP. An analysis of an independent patient set (n=1189) suggested that these two deletions are not founder mutations. Our results suggest that searching for SVs by long-read sequencing in genetically unsolved cases benefits the molecular diagnosis of RP.