ArticleGene2016
Analysis of large-scale whole exome sequencing data to determine the prevalence of genetically-distinct forms of neuronal ceroid lipofuscinosis.
Article in Gene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients.Orphanet journal of rare diseases · 2021Pooled it
- Age at onset and gene variants predict lifespan and disease duration in childhood neuronal ceroid lipofuscinoses.Developmental medicine and child neurology · 2026Article
- A timeline of symptom onset and disease progression in CLN3 disease.Orphanet journal of rare diseases · 2026Review
- Therapeutic antisense oligonucleotide mitigates retinal dysfunction in a pig model of CLN3 Batten disease.Nucleic acids research · 2025Article
- Neuronal Ceroid Lipofuscinosis-Concepts, Classification, and Avenues for Therapy.CNS neuroscience & therapeutics · 2025Review
- Open-label evaluation of oral trehalose in patients with neuronal ceroid lipofuscinoses.Journal of neurology · 2025Article
- GABATranslational psychiatry · 2024Article
- Adverse Reactions to the Orphan Drug Cerliponase Alfa in the Treatment of Neurolipofuscinosis Type 2 (CLN2).Pharmaceuticals (Basel, Switzerland) · 2024Article
- A computational approach to analyzing the functional and structural impacts of Tripeptidyl-Peptidase 1 missense mutations in neuronal ceroid lipofuscinosis.Metabolic brain disease · 2024Article
- Neuronal progenitor cells-based metabolomics study reveals dysregulated lipid metabolism and identifies putative biomarkers for CLN6 disease.Scientific reports · 2023Article
- Protracted CLN3 Batten disease in mice that genetically model an exon-skipping therapeutic approach.Molecular therapy. Nucleic acids · 2023Article
- Clinical and genetic characterization of neuronal ceroid lipofuscinoses (NCLs) in 29 Iranian patients: identification of 11 novel mutations.Human genetics · 2023Article
- Cerebrospinal Fluid Protein Biomarker Discovery in CLN3.Journal of proteome research · 2023Article
- Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview.Frontiers in neurology · 2022Review
- The LINCE Project: A Pathway for Diagnosing NCL2 Disease.Frontiers in pediatrics · 2022Article
- Tripeptidyl Peptidase 1 (TPP1) Deficiency in a 36-Year-Old Patient with Cerebellar-Extrapyramidal Syndrome and Dilated Cardiomyopathy.Life (Basel, Switzerland) · 2021Article
- Therapeutic efficacy of antisense oligonucleotides in mouse models of CLN3 Batten disease.Nature medicine · 2020Article
- Neuronal ceroid lipofuscinosis in the Russian population: Two novel mutations and the prevalence of heterozygous carriers.Molecular genetics & genomic medicine · 2020Article
- Lysosomal protein thermal stability does not correlate with cellular half-life: global observations and a case study of tripeptidyl-peptidase 1.The Biochemical journal · 2020Article
- Mice deficient in the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1) display a complex retinal phenotype.Scientific reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, mostly recessive neurodegenerative lysosomal storage diseases. While clinically similar, they are genetically distinct and result from mutations in at least twelve different genes. Estimates of NCL incidence range from 0.6 to 14 per 100,000 live births but vary widely between populations and are influenced by whether patients are classified based upon clinical or genetic criteria. We investigated mutations in twelve NCL genes in ~61,000 individuals represented in the Exome Aggregation Consortium (ExAC) whole exome sequencing database. Variants were extracted from ExAC and pathogenic alleles were differentiated from neutral polymorphisms using annotated variant databases and missense mutation prediction tools. Carrier frequency was dependent on ethnicity, with the highest (1/75) observed for PPT1 in the Finnish. When data are adjusted for ethnic diversity within the USA, PPT1, TPP1 and CLN3 carrier frequencies were found to be the highest of the NCLs, each at ~1/500. Carrier frequencies calculated from ExAC correlated well with incidence estimated from numbers of living NCL patients in the US. In addition, the analysis identified numerous variants that are annotated as pathogenic in public repositories but have a predicted frequency that is not consistent with patient studies. These variants appear to be neutral polymorphisms that are reported as pathogenic without validation. Based upon literature reports, such alleles may be annotated in public databases as pathogenic and this propagates errors that can have clinical consequences.
Indexed as
Identifiers
What OpenQuestion holds
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.