ArticleEBioMedicine2019
A genetic modifier of symptom onset in Pompe disease.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Are Anti-rhGAA Antibodies a Determinant of Treatment Outcome in Adults with Late-Onset Pompe Disease? A Systematic Review.Biomolecules · 2023Pooled it
- Nociceptive pain in late-onset Pompe disease: prevalence, distribution, and clinical correlates.Journal of neurology · 2026Article
- Managing Pompe Disease and Enzyme Replacement Therapy During Pregnancy: Challenges and Considerations.European journal of neurology · 2026Article
- Pompe Disease: A Review of Diagnosis, Molecular Genetics, and Treatment Management.Current cardiology reviews · 2026Review
- Analysis of the Italian cohort of late-onset Pompe disease (LOPD) patients after 10 and 15 years of therapy with alglucosidase alfa.Journal of neurology · 2025Observational
- Splicing correction by peptide-conjugated morpholinos as a novel treatment for late-onset Pompe disease.Molecular therapy. Nucleic acids · 2025Article
- Rescue of common and rare exon 2 skipping variants of the GAA gene using modified U1 snRNA.Molecular medicine (Cambridge, Mass.) · 2025Article
- Pompe disease: a country-wide molecular screening in a cohort of 15,068 study participants.Frontiers in molecular biosciences · 2025Article
- Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction.Frontiers in genetics · 2025Article
- The European reference network for metabolic diseases (MetabERN) clinical pathway recommendations for Pompe disease (acid maltase deficiency, glycogen storage disease type II).Orphanet journal of rare diseases · 2024Review
- Advances in Pompe Disease Treatment: From Enzyme Replacement to Gene Therapy.Molecular diagnosis & therapy · 2024Review
- Article
- Review
- Biochemical and Genetic Testing of GAA in Over 30.000 Symptomatic Patients Suspected to Be Affected With Pompe Disease.Human mutation · 2024Article
- Light and Shadows in Newborn Screening for Lysosomal Storage Disorders: Eight Years of Experience in Northeast Italy.International journal of neonatal screening · 2023Article
- Muscle ultrasound in patients with late-onset Pompe disease identified by newborn screening.Molecular genetics and metabolism reports · 2023Article
- A Comprehensive Update on Late-Onset Pompe Disease.Biomolecules · 2023Review
- Distribution of Exonic Variants in Glycogen Synthesis and Catabolism Genes in Late Onset Pompe Disease (LOPD).Current issues in molecular biology · 2023Article
- Newborn screening for Pompe disease in Italy: Long-term results and future challenges.Molecular genetics and metabolism reports · 2022Article
- A Newborn with Infantile-Onset Pompe Disease Improving after Administration of Enzyme Replacement Therapy: Case Report.Journal of pediatric intensive care · 2022Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeonatal screening for Pompe disease is complicated by difficulties in predicting symptom onset in patients with the common c.-32-13T>G (IVS1) variant/null (i.e. fully deleterious) acid α-glucosidase (GAA) genotype. This splicing variant occurs in 90% of Caucasian late onset patients, and is associated with a broad range of symptom onset.
methodsWe analyzed a cohort of 143 compound heterozygous and 10 homozygous IVS1 patients, and we assessed ages at symptom onset, the presence of cis-acting single nucleotide variants (SNVs), and performed splicing analysis and enzyme activity assays.
findingsIn compound heterozygous IVS1 patients, the synonymous variant c.510C>T was uniquely present on the IVS1 allele in 9/33 (27%) patients with childhood onset, but was absent from 110 patients with onset in adulthood. GAA enzyme activity was lower in fibroblasts from patients who contained c.510C>T than it was in patients without c.510C>T. By reducing the extent of leaky wild-type splicing, c.510C>T modulated aberrant splicing caused by the IVS1 variant. The deleterious effect of c.510C>T was also found in muscle cells, the main target cells in Pompe disease. In homozygous IVS1 patients, the c.510C>T variant was absent in 4/4 (100%) asymptomatic individuals and present in 3/6 (50%) symptomatic patients. In cells from homozygous IVS1 patients, c.510C>T caused reduced leaky wild-type splicing.
interpretationc.510C>T is a genetic modifier in compound heterozygous and homozygous IVS1 patients. This finding is important for neonatal screening programs for Pompe disease. FUND: This work was funded by grants from Sophia Children's Hospital Foundation (SSWO, grant S17-32) and Metakids (2016-063).
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