RT Journal Article
SR Electronic
T1 Contribution of structural and intronic mutations to <em>RPGRIP1</em>-mediated inherited retinal dystrophies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 211292
DO 10.1101/211292
A1 Farzad Jamshidi
A1 Emily M. Place
A1 Daniel Navarro-Gomez
A1 Mathew Maher
A1 Elise Valkanas
A1 Monkol Lek
A1 Daniel MacArthur
A1 Kinga M. Bujakowska
A1 Eric A. Pierce
YR 2017
UL http://biorxiv.org/content/early/2017/10/30/211292.abstract
AB With the completion of the first phase 3 human gene therapy randomized clinical trial, in the form of voretigene neparvovec for RPE65-mediated inherited retinal dystrophy, as well as the advent of more than 10 other gene therapy trials for inherited retinal disorders, accurate genetic diagnostics will have an increasingly important role in clinical decision-making. Current genetic diagnostic testing panels primarily focus on coding sequences. However, we find that structural and intronic variations are crucial in solving ambiguous cases. We present four families in whom more in depth sequencing and bioinformatic analyses led to the identification of non-coding and structural variations in RPGRIP1 as the cause of disease. In the process we describe ten novel RPGRIP1 mutations. We suggest an expansion of both sequencing and bioinformatics tools in the diagnostics of inherited retinal degenerations to increase sensitivity and to make confident calls before enrolling patients in specific gene therapy clinical trials.