SynthesisOrphanet journal of rare diseases2023
Prognostic value of pathogenic variants in Lafora Disease: systematic review and meta-analysis of patient-level data.
Synthesis in Orphanet journal of rare diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 10 citations in OpenAlex.
- Identification of a Novel homozygous Splice-Site Deletion inPakistan journal of medical sciences · 2026Article
- Exploring the Role of the Laforin/Malin Complex in Rubicon-Dependent Phagocytosis.International journal of molecular sciences · 2026Article
- The challenge of ultra-rarity: Dual diagnosis of Lafora disease and developmental encephalopathies linked to TRIO and SHANK3 pathogenic variants.Epilepsia open · 2025Article
- Neurofilament Light Chain as a Biomarker of Disease Progression in Lafora Disease.Neurology. Genetics · 2025Article
- Seizures and electroencephalographic findings in inborn errors of metabolism: Clues to differential diagnosis in the neonatal period, infancy, childhood and adolescence, and review of the literature.Epileptic disorders : international epilepsy journal with videotape · 2025Review
- The 9th annual Lafora science symposium: a rare epilepsy community makes progress towards clinical readiness.Epilepsy & behavior : E&B · 2025Article
- Case report of Lafora disease: a rare genetic disorder manifesting as progressive myoclonic epilepsy.BMC neurology · 2025Article
- Identification of a pathogenic NHLRC1 variant in a consanguineous Pakistani family affected with severe and rapidly progressive Lafora disease.Acta epileptologica · 2025Article
- Neurological glycogen storage diseases and emerging therapeutics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Clinicopathologic Dissociation: Robust Lafora Body Accumulation in Malin KO Mice Without Observable Changes in Home-Cage Behavior.The Journal of comparative neurology · 2024Article
- Progressive Myoclonus Epilepsy: A Scoping Review of Diagnostic, Phenotypic and Therapeutic Advances.Genes · 2024Article
- Lafora Disease: A Case Report and Evolving Treatment Advancements.Brain sciences · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundLafora disease (LD) is a fatal form of progressive myoclonic epilepsy caused by biallelic pathogenic variants in EPM2A or NHLRC1. With a few exceptions, the influence of genetic factors on disease progression has yet to be confirmed. We present a systematic review and meta-analysis of the known pathogenic variants to identify genotype-phenotype correlations.
methodsWe collected all reported cases with genetically-confirmed LD containing data on disease history. Pathogenic variants were classified into missense (MS) and protein-truncating (PT). Three genotype classes were defined according to the combination of the variants: MS/MS, MS/PT, and PT/PT. Time-to-event analysis was performed to evaluate survival and loss of autonomy.
results250 cases described in 70 articles were included. The mutated gene was NHLRC1 in 56% and EPM2A in 44% of cases. 114 pathogenic variants (67 EPM2A; 47 NHLRC1) were identified. The NHLRC1 genotype PT/PT was associated with shorter survival [HR 2.88; 95% CI 1.23-6.78] and a trend of higher probability of loss of autonomy [HR 2.03, 95% CI 0.75-5.56] at the multivariable Cox regression analysis. The population carrying the homozygous p.Asp146Asn variant of NHLRC1 genotype was confirmed to have a more favourable prognosis in terms of disease duration.
conclusionsThis study demonstrates the existence of prognostic genetic factors in LD, namely the genotype defined according to the functional impact of the pathogenic variants. Although the reasons why NHLRC1 genotype PT/PT is associated with a poorer prognosis have yet to be fully elucidated, it may be speculated that malin plays a pivotal role in LD pathogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.