ArticleJournal of human genetics2020
The clinical-phenotype continuum in DYNC1H1-related disorders-genomic profiling and proposal for a novel classification.
Article in Journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Synthetic cargo adaptors reveal molecular features that enhance dynein activation.Nature communications · 2026Article
- Landscape of parental postzygotic mutations across >11,000 rare disease trios.American journal of human genetics · 2026Article
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- DYNC1H1 in Spinal Muscular Atrophy: Diagnostic Findings From Two Families and a Comprehensive Review of Its Role in Neuromuscular and Neurodevelopmental Disorders.Molecular genetics & genomic medicine · 2025Review
- Neuroaxonal Degeneration as a Converging Mechanism in Motor Neuron Diseases (MNDs): Molecular Insights into RNA Dysregulation and Emerging Therapeutic Targets.International journal of molecular sciences · 2025Review
- Analysis of theGenes · 2025Article
- Glial Cells in Spinal Muscular Atrophy: Speculations on Non-Cell-Autonomous Mechanisms and Therapeutic Implications.Neurology international · 2025Review
- Dynein-driven regulation of postsynaptic membrane architecture and synaptic function.Journal of cell science · 2025Article
- The expanding clinical and genetic spectrum of DYNC1H1-related disorders.Brain : a journal of neurology · 2025Article
- Neuroradiologic, Clinical, and Genetic Characterization of Cerebellar Heterotopia: A Pediatric Multicentric Study.AJNR. American journal of neuroradiology · 2025Article
- Engine breakdown of lysosomes and related organelles and the resulting physiology.Frontiers in cell and developmental biology · 2025Review
- The space-time continuum in neurological disorders of the autophagosome-lysosome fusion machinery.Autophagy reports · 2025Review
- Clinical and Genetic Profiles of 5q- and Non-5q-Spinal Muscular Atrophy Diseases in Pediatric Patients.Genes · 2024Review
- Patient-specific mutation of Dync1h1 in mice causes brain and behavioral deficits.Neurobiology of disease · 2024Article
- A novel mutation in SORD gene associated with distal hereditary motor neuropathies.BMC medical genomics · 2024Article
- Spinal Muscular Atrophy with Predominant Lower Extremity (SMA-LED) with Intellectual Disability and Dysmorphism.Indian journal of pediatrics · 2024Article
- Review
- Comparative Hippocampal Proteome and Phosphoproteome in a Niemann-Pick, Type C1 Mouse Model Reveal Insights into Disease Mechanisms.Journal of proteome research · 2024Article
- Novel Genetic and Phenotypic Expansion inGenes · 2023Article
- Genetic Primary Microcephalies: When Centrosome Dysfunction Dictates Brain and Body Size.Cells · 2023Review
Corrections and comments
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Authors and funding
18 authors at 10 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the cytoplasmic dynein 1 heavy chain gene (DYNC1H1) have been identified in rare neuromuscular (NMD) and neurodevelopmental (NDD) disorders such as spinal muscular atrophy with lower extremity dominance (SMALED) and autosomal dominant mental retardation syndrome 13 (MRD13). Phenotypes and genotypes of ten pediatric patients with pathogenic DYNC1H1 variants were analyzed in a multi-center study. Data mining of large-scale genomic variant databases was used to investigate domain-specific vulnerability and conservation of DYNC1H1. We identified ten patients with nine novel mutations in the DYNC1H1 gene. These patients exhibit a broad spectrum of clinical findings, suggesting an overlapping disease manifestation with intermixed phenotypes ranging from neuropathy (peripheral nervous system, PNS) to severe intellectual disability (central nervous system, CNS). Genomic profiling of healthy and patient variant datasets underlines the domain-specific effects of genetic variation in DYNC1H1, specifically on toleration towards missense variants in the linker domain. A retrospective analysis of all published mutations revealed domain-specific genotype-phenotype correlations, i.e., mutations in the dimerization domain with reductions in lower limb strength in DYNC1H1-NMD and motor domain with cerebral malformations in DYNC1H1-NDD. We highlight that the current classification into distinct disease entities does not sufficiently reflect the clinical disease manifestation that clinicians face in the diagnostic work-up of DYNC1H1-related disorders. We propose a novel clinical classification for DYNC1H1-related disorders encompassing a spectrum from DYNC1H1-NMD with an exclusive PNS phenotype to DYNC1H1-NDD with concomitant CNS involvement.
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