Recent OGI Publications

June 12, 2020

AAV-Mediated Gene Augmentation Therapy Restores Critical Functions in Mutant PRPF31^+/− iPSC-Derived RPE Cells

Elizabeth M. Brydon¹³Revital Bronstein¹³Adriana Buskin²Majlinda Lako²Eric A. Pierce¹Rosario Fernandez-Godino¹

Mutations in the PRPF31 gene account for 10% of dominant retinitis pigmentosa (RP), which is the most common kind of inherited blindness.

This publication uses retinal cells derived from induced pluripotent stem cells as a proof-of-concept that AAV-based gene therapy can be used for treatment of PRPF31-associated RP.

Expanding the phenotypic spectrum in RDH12-associated retinal disease

Scott HA, Place EM, Ferenchak K, Zampaglione E, Wagner NE, Chao KR, DiTroia SP, Navarro-Gomez D, Mukai S, Huckfeldt RM, Pierce EA, Bujakowska KM. Cold Spring Harb Mol Case Stud. 2020 Feb 3;6(1). pii: a004754. doi: 10.1101/mcs.a004754. Print 2020 Feb.

Our recent paper “Expanding the phenotypic spectrum of RDH12-associated retinal disease” describes eleven inherited retinal degeneration (IRD) patients with bi-allelic mutations in RDH12 that display a range of phenotypic severity. 

Traditionally mutations in RDH12 were only screened in severe cases of IRD potentially missing patients with milder disease, however broad genetic testing allowed the diagnosis of two patients with macular dystrophy in this study.  Given the wide phenotypic spectrum of RDH12 disease, we advocate for more robust approach with targeted panel testing of all known IRD genes to provide accurate genetic diagnosis.

In addition, we describe 15 causal alleles including four novel variants that contribute to the catalog of RDH12 mutations to aid in genetic diagnosis of RDH12-associated retinal disease.

Copy-number variation contributes 9% of pathogenicity in the inherited retinal degenerations.

Zampaglione E, Kinde B, Place EM, Navarro-Gomez D, Maher M, Jamshidi F, Nassiri S, Mazzone JA, Finn C, Schlegel D, Comander J, Pierce EA, Bujakowska KM.Genet Med. 2020 Feb 10. doi: 10.1038/s41436-020-0759-8. [Epub ahead of print]

In this study, we showed that some previously unsolved inherited retinal disease (IRD) cases were caused by copy number variations (CNVs) in the known genes.

We analyzed a cohort of 500 IRD patients, solving 55.6% of the cases with an initial single nucleotide variant (SNV) analysis. We then looked for potentially causal CNVs, comparing three methods: two sequencing based prediction algorithms, gCNV and ExomeDepth, and a more conventional SNP-array based method.

We found that of the three approaches, gCNV performed the best, and that adding CNV analysis to our pipeline improved our IRD solving rate by 10.2%.