ArticleHuman genetics2016
Genetic heterogeneity in 26 infants with a hypomyelinating leukodystrophy.
Article in Human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 34 citations in OpenAlex.
- Expanding the phenotypic and genotypic spectrum ofBrain communications · 2026Article
- Electrophysiological characterization of human KCNT1 channel modulators and the therapeutic potential of hydroquinine and tipepidine in KCNT1 mutation-associated epilepsy mouse model.Acta pharmacologica Sinica · 2025Article
- Neuroimaging to Genotype: Delineating the Spectrum of Disorders With Deficient Myelination in the Indian Population.American journal of medical genetics. Part A · 2025Article
- The natural history of variable subtypes in pediatric-onset TUBB4A-related leukodystrophy.Molecular genetics and metabolism · 2025Article
- Understanding molecular mechanisms and predicting phenotypic effects of pathogenic tubulin mutations.PLoS computational biology · 2022Article
- In-silico phenotype prediction by normal mode variant analysis in TUBB4A-related disease.Scientific reports · 2022Article
- The Slack Channel Deletion Causes Mechanical Pain Hypersensitivity in Mice.Frontiers in molecular neuroscience · 2022Article
- Hypomyelinating leukodystrophies - unravelling myelin biology.Nature reviews. Neurology · 2021Review
- Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?Frontiers in cellular neuroscience · 2021Review
- Microtubule Dysfunction: A Common Feature of Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- Phactr1 regulates Slack (KCNT1) channels via protein phosphatase 1 (PP1).FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Functional consequences of a KCNT1 variant associated with status dystonicus and early-onset infantile encephalopathy.Annals of clinical and translational neurology · 2019Article
- Canine NAPEPLD-associated models of human myelin disorders.Scientific reports · 2018Article
- Clinical and molecular characterization ofNeurology · 2018Article
- Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients.PloS one · 2018Article
- TUBB4A mutations result in specific neuronal and oligodendrocytic defects that closely match clinically distinct phenotypes.Human molecular genetics · 2017Article
- A novelHuman genome variation · 2017Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T2 hyperintensity of brain white matter lesions detected by magnetic resonance imaging (MRI) are characteristic of a heterogeneous group of diseases. Persistent T2 high intensity in combination with T1 iso- or high intensity of white matter in infants indicates a lack of normal myelination, that is, hypomyelination. However, the precise diagnosis of hypomyelinating leukodystrophy based solely on MRI findings can be difficult, especially in the early stage of the disease. We studied 26 patients who were diagnosed with hypomyelinating leukodystrophy according to MRI findings and clinical features to uncover their genetic etiology through chromosomal analyses, targeted gene analyses, and an array comparative genomic hybridization (aCGH) assay. Then, for the 17 patients with unexplained hypomyelination by traditional analyses, whole-exome sequencing (WES) was performed. The presumptive diagnoses were confirmed in 58 % of the enrolled patients (15/26) and involved 9 different genetic backgrounds. The most frequent backgrounds were 18q deletion syndrome and Pelizaeus-Merzbacher disease, with an incidence of 12 % (3/26) for both. The diagnostic rate of chromosomal analyses, targeted gene analyses, and aCGH was 31 % (8/26), and one patient was clinically diagnosed with Cockayne syndrome. Using WES, the following causative genes of hypomyelination were identified in six individuals (35 %, 6/17): TUBB4A, POLR3B, KCNT1, and MCOLN1, and some of those genes were pathogenic for not only hypomyelination but also dysmyelination or delayed myelination. Our findings suggested heterogeneous genetic backgrounds in patients with persistent white matter lesions. These data also indicate that WES may be a rapid and useful tool for identifying the underlying genetic causes of undiagnosed leukodystrophies.
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