ArticlePediatric neurology2020
Elevated Leukodystrophy Incidence Predicted From Genomics Databases.
Article in Pediatric neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Cognitive and intellectual functioning in leukodystrophy patients: a systematic review.Orphanet journal of rare diseases · 2025Pooled it
- Inpatient Deaths in Pediatric Leukodystrophies.Annals of the Child Neurology Society · 2026Article
- Rigorous genetic diagnosis review in natural history studies.Orphanet journal of rare diseases · 2026Article
- Developing a National Network for Leukodystrophy Research and Care in Canada: The CARELeuko Initiative.Neurology. Genetics · 2025Review
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Case Report: New genetic variant and widely different phenotypes observed in twins with Vanishing White Matter disease.Frontiers in pediatrics · 2025Article
- Towards a Treatment for Leukodystrophy Using Cell-Based Interception and Precision Medicine.Biomolecules · 2024Review
- Novel Pathogenic Variants inHuman mutation · 2024Article
- Hypomyelination, hypodontia and craniofacial abnormalities in a Polr3b mouse model of leukodystrophy.Brain : a journal of neurology · 2023Article
- Craniofacial features of POLR3-related leukodystrophy caused by biallelic variants inJournal of medical genetics · 2023Article
- Core protocol development for phase 2/3 clinical trials in the leukodystrophy vanishing white matter: a consensus statement by the VWM consortium and patient advocates.BMC neurology · 2023Article
- Biallelic pathogenic variants inFrontiers in neurology · 2023Article
- Incidence of Aicardi-Goutières syndrome andMolecular genetics and metabolism reports · 2022Article
- Early recognition of patients with leukodystrophies.Current problems in pediatric and adolescent health care · 2022Review
- Antisense Oligonucleotide Therapy for the Nervous System: From Bench to Bedside with Emphasis on Pediatric Neurology.Pharmaceutics · 2022Review
- [Research advances in the clinical genetics of leukodystrophy in children].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2022Review
- Therapy Trial Design in Vanishing White Matter: An Expert Consortium Opinion.Neurology. Genetics · 2022Review
- Case Report: A NovelFrontiers in genetics · 2022Article
- Hospitalization Burden and Incidence of Krabbe Disease.Journal of child neurology · 2022Article
- The White Matter Rounds experience: The importance of a multidisciplinary network to accelerate the diagnostic process for adult patients with rare white matter disorders.Frontiers in neurology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundLeukodystrophies are genetic diseases affecting the white matter and leading to early death. Our objective was to determine leukodystrophy incidence, using genomics sequencing databases allele frequencies of disease-causing variants.
methodsFrom 49 genes, representing the standardly defined group of leukodystrophies, we identified potential disease-causing variants from publications in the Human Genetic Mutation Database and from predictions in the Genome Aggregation Database. Allele frequencies were estimated from Genome Aggregation Database. Allele frequencies for each gene were summed to generate a super allele frequency and we used the Hardy-Weinberg equation to calculate overall expected live birth incidence associated with the gene in question.
resultsWe identified 4564 pathogenic variants for 25 discrete leukodystrophies. The largest effect was from GALC variants (Krabbe disease), which had a predicted incidence of one in 12,080 live births, 8.3 times higher than published estimates. The second most frequently predicted leukodystrophy was the RNA polymerase III-related disorders, which had an incidence of 1:26,160. Overall, we found a leukodystrophy incidence of 1 in 4733 live births, significantly higher than previous estimates.
conclusionsOur data are consistent with a significant underdiagnosis of leukodystrophy patients. An intriguing additional consideration is that there may be genetic modifiers that lead to weaker, absent, or adult-onset disease phenotypes.
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Registered trials
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.