Cell modeling and rescue of a novel noncoding genetic cause of glycogen storage disease IX
As evidenced by RNA sequencing, population and allelic segregation data, and phenotyping of an isogenic cell culture model of the variant, we concluded that <i>PHKG2</i> c.556+1069T>G causes GSD IX γ2 and can be targeted using antisense oligonucleotides. This demonstrates a novel and robust pathway for detecting, validating, and reversing the impacts of noncoding causes of rare disease.
Authors
- Alexias Safi
- Timothy E. Reddy (ORCID: https://orcid.org/0000-0002-7629-061X)
- Catherine Rehder (ORCID: https://orcid.org/0000-0003-4924-9010)
- Andrew S. Allen (ORCID: https://orcid.org/0000-0002-7232-2143)
- Apoorva K. Iyengar (ORCID: https://orcid.org/0000-0001-8465-333X)
- Karynne Patterson (ORCID: https://orcid.org/0000-0002-0853-1231)
- Priya Sunil Kishnani (ORCID: https://orcid.org/0000-0001-8251-909X)
- Gregory E. Crawford (ORCID: https://orcid.org/0000-0001-6106-2772)
- R. A. Francis
- Rebecca L. Koch (ORCID: https://orcid.org/0000-0002-5387-3185)
- M. Makenzie Beaman (ORCID: https://orcid.org/0000-0003-4066-2060)
- Shruthi Mohan (ORCID: https://orcid.org/0000-0002-2796-282X)
- Deeksha Bali (ORCID: https://orcid.org/0000-0003-2550-8073)
- Michael J. Bamshad (ORCID: https://orcid.org/0000-0002-9647-0861)
- Jessica X. Chong (ORCID: https://orcid.org/0000-0002-1616-2448)
- William H. Majoros (ORCID: https://orcid.org/0000-0001-7284-9335)
- Xue Zou (ORCID: https://orcid.org/0000-0002-0512-1341)
- Jian Dai (ORCID: https://orcid.org/0009-0002-1508-8140)
- Shannon Clarke (ORCID: https://orcid.org/0009-0008-8261-7640)
Institutions
- Seattle Children's Hospital (US)
- Statistical and Applied Mathematical Sciences Institute (US)
- Duke University (US)
- University of Washington (US)
- Altius Institute for Biomedical Sciences (US)
- Brotman Baty Institute (US)
- Duke University Health System (US)
Publication Details
- Journal
- Genetics in Medicine Open
- Published
- 2025-11-20
- DOI
- https://doi.org/10.1016/j.gimo.2025.103474
- Primary Topic
- Glycogen Storage Diseases and Myoclonus
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health