ArticleAmerican journal of human genetics2021
Progressive myoclonus epilepsies-Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes.
Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 83 citations in OpenAlex.
- Novel NUS1 variant in a Chinese patient with progressive myoclonus epilepsy: a case report and systematic review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Pooled it
- N-Type Ca Channel in Epileptic Syndromes and Epilepsy: A Systematic Review of Its Genetic Variants.International journal of molecular sciences · 2023Pooled it
- Clinical and molecular spectrum of congenital disorders of glycosylation in 80 Egyptian patients.Human genetics · 2026Article
- AProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Evolutionary divergence and functional insights into the heteromeric cis-prenyltransferase of Paramecium tetraurelia.The FEBS journal · 2026Article
- Deficiency of the NAD(P)HX metabolic repair system: a treatable mitochondrial disease.Orphanet journal of rare diseases · 2026Article
- Case Report: Recurrent pathogenic mutation c.110G>A inFrontiers in neuroscience · 2026Article
- Zellweger syndrome; identification of mutations inAnnals of medicine · 2025Article
- Structural mechanisms of allosteric regulation in the human cis-prenyltransferase complex.Nature communications · 2025Article
- Fundamental Neurochemistry Review: Sphingolipids and Ceramides in Brain Development.Journal of neurochemistry · 2025Review
- The Spectrum of Neurologic Phenotypes Associated With NUS1 Pathogenic Variants: A Comprehensive Case Series.Annals of neurology · 2025Article
- Progressive Myoclonus Epilepsy: Distinctive MRI Changes in Cerebellar and Motor Networks.Annals of clinical and translational neurology · 2025Article
- Phenotypic diversity in NAXE mutations.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Monogenic Epilepsies in Adult Epilepsy Clinics and Gene-Driven Approaches to Treatment.Current neurology and neuroscience reports · 2025Review
- Genetic epilepsies with myoclonic seizures: Mechanisms and syndromes.Epilepsia open · 2025Review
- Copy number variant analysis improves diagnostic yield in a diverse pediatric exome sequencing cohort.NPJ genomic medicine · 2025Article
- Niemann-Pick C-like Endolysosomal Dysfunction in DHDDS Patient Cells, a Congenital Disorder of Glycosylation, Can Be Treated with Miglustat.International journal of molecular sciences · 2025Article
- Genome-Wide Association Study of Temporomandibular Disorder-Related Pain in Finnish Populations.Journal of oral rehabilitation · 2025Article
- Spinal muscular atrophy with progressive myoclonic epilepsy: A case report from China with newHeliyon · 2025Article
- Novel, complex configurations of theBrain communications · 2025Article
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39 authors at 20 institutions in 10 countries.
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Abstract
Progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous rare diseases. Over 70% of PME cases can now be molecularly solved. Known PME genes encode a variety of proteins, many involved in lysosomal and endosomal function. We performed whole-exome sequencing (WES) in 84 (78 unrelated) unsolved PME-affected individuals, with or without additional family members, to discover novel causes. We identified likely disease-causing variants in 24 out of 78 (31%) unrelated individuals, despite previous genetic analyses. The diagnostic yield was significantly higher for individuals studied as trios or families (14/28) versus singletons (10/50) (OR = 3.9, p value = 0.01, Fisher's exact test). The 24 likely solved cases of PME involved 18 genes. First, we found and functionally validated five heterozygous variants in NUS1 and DHDDS and a homozygous variant in ALG10, with no previous disease associations. All three genes are involved in dolichol-dependent protein glycosylation, a pathway not previously implicated in PME. Second, we independently validate SEMA6B as a dominant PME gene in two unrelated individuals. Third, in five families, we identified variants in established PME genes; three with intronic or copy-number changes (CLN6, GBA, NEU1) and two very rare causes (ASAH1, CERS1). Fourth, we found a group of genes usually associated with developmental and epileptic encephalopathies, but here, remarkably, presenting as PME, with or without prior developmental delay. Our systematic analysis of these cases suggests that the small residuum of unsolved cases will most likely be a collection of very rare, genetically heterogeneous etiologies.
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