ArticleAmerican journal of human genetics2012
A nonsense mutation in DHTKD1 causes Charcot-Marie-Tooth disease type 2 in a large Chinese pedigree.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Genetic Architecture of Plasma Alpha-Aminoadipic Acid Reveals a Relationship With High-Density Lipoprotein Cholesterol.Journal of the American Heart Association · 2022Pooled it
- Aminoadipate-semialdehyde synthase, a potential target for substrate reduction therapy in glutaric aciduria type 1.Scientific reports · 2026Article
- Metabolite 2-aminoadipic acid: implications for metabolic disorders and therapeutic opportunities.Frontiers in pharmacology · 2025Review
- A novel DHTKD1 variant is associated with an atypical form of Charcot-Marie-Tooth disease type 2Q?Acta neurologica Belgica · 2024Article
- Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.Sub-cellular biochemistry · 2024Review
- Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity.Genome medicine · 2023Article
- Neuronal RBM5 modulates cell signaling responses to traumatic and hypoxic-ischemic injury in a sex-dependent manner.Cell death discovery · 2023Article
- Review
- Characterization of genome-wide STR variation in 6487 human genomes.Nature communications · 2023Article
- Probing the E1o-E2o and E1a-E2o Interactions in Binary Subcomplexes of the Human 2-Oxoglutarate Dehydrogenase and 2-Oxoadipate Dehydrogenase Complexes by Chemical Cross-Linking Mass Spectrometry and Molecular Dynamics Simulation.International journal of molecular sciences · 2023Article
- The Brain Protein Acylation System Responds to Seizures in the Rat Model of PTZ-Induced Epilepsy.International journal of molecular sciences · 2022Article
- Functional Versatility of the Human 2-Oxoadipate Dehydrogenase in the L-Lysine Degradation Pathway toward Its Non-Cognate Substrate 2-Oxopimelic Acid.International journal of molecular sciences · 2022Article
- Administration of Phosphonate Inhibitors of Dehydrogenases of 2-Oxoglutarate and 2-Oxoadipate to Rats Elicits Target-Specific Metabolic and Physiological Responses.Frontiers in chemistry · 2022Article
- Delayed Impact of 2-Oxoadipate Dehydrogenase Inhibition on the Rat Brain Metabolism Is Linked to Protein Glutarylation.Frontiers in medicine · 2022Article
- HeterozygousGenes · 2021Article
- NADGenes · 2021Review
- Toward an Understanding of the Structural and Mechanistic Aspects of Protein-Protein Interactions in 2-Oxoacid Dehydrogenase Complexes.Life (Basel, Switzerland) · 2021Review
- Knock-Out ofFrontiers in endocrinology · 2021Article
- Inhibition and Crystal Structure of the Human DHTKD1-Thiamin Diphosphate Complex.ACS chemical biology · 2020Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Charcot-Marie-Tooth (CMT) disease represents a clinically and genetically heterogeneous group of inherited neuropathies. Here, we report a five-generation family of eight affected individuals with CMT disease type 2, CMT2. Genome-wide linkage analysis showed that the disease phenotype is closely linked to chromosomal region 10p13-14, which spans 5.41 Mb between D10S585 and D10S1477. DNA-sequencing analysis revealed a nonsense mutation, c.1455T>G (p.Tyr485(∗)), in exon 8 of dehydrogenase E1 and transketolase domain-containing 1 (DHTKD1) in all eight affected individuals, but not in other unaffected individuals in this family or in 250 unrelated normal persons. DHTKD1 mRNA expression levels in peripheral blood of affected persons were observed to be half of those in unaffected individuals. In vitro studies have shown that, compared to wild-type mRNA and DHTKD1, mutant mRNA and truncated DHTKD1 are significantly decreased by rapid mRNA decay in transfected cells. Inhibition of nonsense-mediated mRNA decay by UPF1 silencing effectively rescued the decreased levels of mutant mRNA and protein. More importantly, DHTKD1 silencing was found to lead to impaired energy production, evidenced by decreased ATP, total NAD(+) and NADH, and NADH levels. In conclusion, our data demonstrate that the heterozygous nonsense mutation in DHTKD1 is one of CMT2-causative genetic alterations, implicating an important role for DHTKD1 in mitochondrial energy production and neurological development.
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.