ArticleAmerican journal of human genetics2017
Mutations in NKX6-2 Cause Progressive Spastic Ataxia and Hypomyelination.
Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- A Meta-Analysis of the Converging Effects of Different Classes of Antipsychotics on the Frontal Cortex Transcriptome in Laboratory Rodents and Non-Human Primates.bioRxiv : the preprint server for biology · 2026Article
- Distinct transcriptomic and epigenomic responses of mature oligodendrocytes during disease progression in a mouse model of multiple sclerosis.Nature neuroscience · 2025Article
- MRI Insights in Hypomyelinating Disorders With Early Myelination Disturbances.Neurology. Genetics · 2024Article
- ITPR2 Mediated Calcium Homeostasis in Oligodendrocytes is Essential for Myelination and Involved in Depressive-Like Behavior in Adolescent Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Occupational Therapy Intervention in the Child with Leukodystrophy: Case Report.Children (Basel, Switzerland) · 2023Article
- Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers.Nature communications · 2023Article
- Identification of a de novo Mutation in TMEM106B in a Saudi Child Causes Hypomyelination Leukodystrophy.Global medical genetics · 2023Article
- Functional investigation of SLC1A2 variants associated with epilepsy.Cell death & disease · 2022Article
- A Diagnostic Approach to Spastic ataxia Syndromes.Cerebellum (London, England) · 2022Review
- Identification of a Novel Renal Metastasis Associated CpG-Based DNA Methylation Signature (RMAMS).International journal of molecular sciences · 2022Article
- Disrupted myelination network in the cingulate cortex of Parkinson's disease.IET systems biology · 2022Article
- Emerging cellular themes in leukodystrophies.Frontiers in cell and developmental biology · 2022Review
- Variants inHGG advances · 2021Article
- Hypomyelinating leukodystrophies - unravelling myelin biology.Nature reviews. Neurology · 2021Review
- CoExp: A Web Tool for the Exploitation of Co-expression Networks.Frontiers in genetics · 2021Article
- Spastic paraplegia precedingAlzheimer's & dementia (Amsterdam, Netherlands) · 2021Article
- Analyzing Gene Expression Profiles from Ataxia and Spasticity Phenotypes to Reveal Spastic Ataxia Related Pathways.International journal of molecular sciences · 2020Article
- CNP deficiency causes severe hypomyelinating leukodystrophy in humans.Human genetics · 2020Article
- Genetic and phenotypic characterization of NKX6-2-related spastic ataxia and hypomyelination.European journal of neurology · 2020Article
- Bu-Shen-Yi-Sui Capsule, an Herbal Medicine Formula, Promotes Remyelination by Modulating the Molecular Signals via Exosomes in Mice with Experimental Autoimmune Encephalomyelitis.Oxidative medicine and cellular longevity · 2020Article
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Authors and funding
17 authors at 5 institutions in 5 countries.
Funding
Abstract
Progressive limb spasticity and cerebellar ataxia are frequently found together in clinical practice and form a heterogeneous group of degenerative disorders that are classified either as pure spastic ataxia or as complex spastic ataxia with additional neurological signs. Inheritance is either autosomal dominant or autosomal recessive. Hypomyelinating features on MRI are sometimes seen with spastic ataxia, but this is usually mild in adults and severe and life limiting in children. We report seven individuals with an early-onset spastic-ataxia phenotype. The individuals come from three families of different ethnic backgrounds. Affected members of two families had childhood onset disease with very slow progression. They are still alive in their 30s and 40s and show predominant ataxia and cerebellar atrophy features on imaging. Affected members of the third family had a similar but earlier-onset presentation associated with brain hypomyelination. Using a combination of homozygozity mapping and exome sequencing, we mapped this phenotype to deleterious nonsense or homeobox domain missense mutations in NKX6-2. NKX6-2 encodes a transcriptional repressor with early high general and late focused CNS expression. Deficiency of its mouse ortholog results in widespread hypomyelination in the brain and optic nerve, as well as in poor motor coordination in a pattern consistent with the observed human phenotype. In-silico analysis of human brain expression and network data provides evidence that NKX6-2 is involved in oligodendrocyte maturation and might act within the same pathways of genes already associated with central hypomyelination. Our results support a non-redundant developmental role of NKX6-2 in humans and imply that NKX6-2 mutations should be considered in the differential diagnosis of spastic ataxia and hypomyelination.
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