Genotype and Phenotype Description in Individuals With GYG1 Variants—A Case Report and Systematic Review
6 affiliations
- 1Division of Genetic Medicine University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL) Lausanne Switzerland
- 2Service of Endocrinology, Diabetes and Metabolism University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL) Lausanne Switzerland
- 3Medical Library University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL) Lausanne Switzerland
- 4Institute of Pathology University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL) Lausanne Switzerland
- 5Department of Cardiology University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL) Lausanne Switzerland
- 6Department of Clinical Neurosciences, Service of Neurology, Nerve‐Muscle Unit University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL) Lausanne Switzerland
Abstract
Glycogen Storage Disease Type XV (GSD XV) is a rare autosomal recessive disorder caused by biallelic pathogenic variants in GYG1, encoding glycogenin‐1. Although primarily a myopathic disease, cardiac involvement is increasingly recognized and overlapping features with other neuromuscular disorders contribute to underdiagnosis. We performed a systematic search of databases without restrictions on publication dates. Twenty‐one articles describing individuals with GSD XV were included, providing clinical, histological, and genetic data. In addition to the systematic review, we present an illustrative case of GSD XV diagnosed at our institution. We identified 49 individuals, of whom 98% were symptomatic with onset ranging from childhood to late adulthood; manifestations were isolated neuromuscular (81.6%), cardiac (8.2%), or mixed (8.2%). One case (2.0%) was asymptomatic. Among neuromuscular cases, 12% required a walking aid, while four cardiac patients required implantable cardioverter‐defibrillators and two underwent heart transplantation. Muscle biopsy frequently revealed PAS‐positive, diastase‐resistant polyglucosan bodies, although polyglucosan bodies were not consistently identified by electron microscopy. Molecular diagnosis was confirmed in all cases, with c.143+3G>C in GYG1 being the most prevalent variant, homozygous in 36.7% of patients and associated with both juvenile and adult‐onset phenotypes. GSD XV should be considered in cases with unexplained myopathy or cardiomyopathy, regardless of age at onset. Genetic testing remains the gold standard for diagnosis, although muscle biopsy can guide investigations, particularly in atypical cases or when genetic analysis is inconclusive. Further studies are needed to clarify the full clinical spectrum, refine genotype–phenotype correlations, and guide long‐term management strategies.
Related
- Genotype-phenotype single-cell transcriptomics for massive parallel assessment of genetic variants
- Muscular phenotype description of abnormal THOC2 splicing
- Genotype-Phenotype Correlations Reveal Positive Inheritance and Phenotype Associations for PROM1-Associated Inherited Retinal Degenerations
- Hereditary Breast Cancer in a Brazilian Referral Cohort: Germline Diversity and Genotype–Phenotype Associations
- Genotype-phenotype studies in neurosensory diseases: a blood based personalized disease modeling platform for neurosensory hearing loss
BibTeX
@article{schadeck2026genotype,
title = {{Genotype and Phenotype Description in Individuals With GYG1 Variants—A Case Report and Systematic Review}},
author = {M. Schadeck and A. Tankeu and J. Elmers and E. Hewer and F. Maurer and P. Monney and M. Théaudin and C. Tran},
journal = {JIMD Reports},
year = {2026},
month = nov,
doi = {10.1002/jmd2.70134},
url = {https://doi.org/10.1002/jmd2.70134},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Genotype and Phenotype Description in Individuals With GYG1 Variants—A Case Report and Systematic Review
AU - M. Schadeck
AU - A. Tankeu
AU - J. Elmers
AU - E. Hewer
AU - F. Maurer
AU - P. Monney
AU - M. Théaudin
AU - C. Tran
PY - 2026
DA - 2026/11/05
JO - JIMD Reports
DO - 10.1002/jmd2.70134
UR - https://doi.org/10.1002/jmd2.70134
AB - Glycogen Storage Disease Type XV (GSD XV) is a rare autosomal recessive disorder caused by biallelic pathogenic variants in GYG1, encoding glycogenin‐1. Although primarily a myopathic disease, cardiac involvement is increasingly recognized and overlapping features with other neuromuscular disorders contribute to underdiagnosis. We performed a systematic search of databases without restrictions on publication dates. Twenty‐one articles describing individuals with GSD XV were included, providing clinical, histological, and genetic data. In addition to the systematic review, we present an illustrative case of GSD XV diagnosed at our institution. We identified 49 individuals, of whom 98% were symptomatic with onset ranging from childhood to late adulthood; manifestations were isolated neuromuscular (81.6%), cardiac (8.2%), or mixed (8.2%). One case (2.0%) was asymptomatic. Among neuromuscular cases, 12% required a walking aid, while four cardiac patients required implantable cardioverter‐defibrillators and two underwent heart transplantation. Muscle biopsy frequently revealed PAS‐positive, diastase‐resistant polyglucosan bodies, although polyglucosan bodies were not consistently identified by electron microscopy. Molecular diagnosis was confirmed in all cases, with c.143+3G>C in GYG1 being the most prevalent variant, homozygous in 36.7% of patients and associated with both juvenile and adult‐onset phenotypes. GSD XV should be considered in cases with unexplained myopathy or cardiomyopathy, regardless of age at onset. Genetic testing remains the gold standard for diagnosis, although muscle biopsy can guide investigations, particularly in atypical cases or when genetic analysis is inconclusive. Further studies are needed to clarify the full clinical spectrum, refine genotype–phenotype correlations, and guide long‐term management strategies.
SN - 2192-8304
SN - 2192-8312
ER -