<i>UDP‐glucose dehydrogenase</i> variants cause dystroglycanopathy
UDP-glucose dehydrogenase (UGDH) variants have been associated with hypotonia, developmental delay, and epilepsy. We report the first pathologic evidence of dystroglycanopathy in siblings with UGDH variants. Both presented around 6 months with developmental delay and elevated creatinine kinase. Sibling A developed epilepsy at age 9 years. Muscle biopsy from sibling A showed necrotizing myopathy with reduced matriglycan immunostaining. Western blot revealed α-dystroglycan with abnormally low molecular weight. The siblings shared pathogenic UGDH variants in trans: c.305G>A p.(R102Q) is predicted to disrupt protein structure and function; c.265-6C>G is deleterious to splicing. We propose that UGDH is an additional dystroglycanopathy gene.
Authors
- Anna Reelfs
- Theresa Czech (ORCID: https://orcid.org/0000-0003-4431-2017)
- Steven A. Moore (ORCID: https://orcid.org/0000-0002-6353-7900)
- Katherine D. Mathews (ORCID: https://orcid.org/0000-0003-4160-0435)
- Soumya Joseph (ORCID: https://orcid.org/0000-0002-0487-1378)
- Benjamin W. Darbro (ORCID: https://orcid.org/0000-0001-9279-356X)
- Mary O. Cox
- Carrie Stephan (ORCID: https://orcid.org/0000-0001-5782-4957)
- Kevin P. Campbell (ORCID: https://orcid.org/0000-0003-2066-5889)
Institutions
- University of Iowa (US)
- Howard Hughes Medical Institute (US)
Publication Details
- Journal
- Annals of Clinical and Translational Neurology
- Published
- 2025-04-17
- DOI
- https://doi.org/10.1002/acn3.70002
- Citations
- 3
- Primary Topic
- Metabolism, Diabetes, and Cancer
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke