Cited by 156DNA Repair MechanismsGenomics and Rare DiseasesGenetic Neurodegenerative Diseases

Neuropathology of Cockayne syndrome: Evidence for impaired development, premature aging, and neurodegeneration

Weidenheim, Karen M., Dickson, Dennis W., Rapin, Isabelle·2009·Mechanisms of Ageing and Development

Abstract

Global growth and development failure, premature, accelerated, pathologic aging, and neurodegeneration characterize Cockayne syndrome (CS) and the cerebro-oculo-facial-skeletal and xeroderma pigmentosum/CS syndromes which overlap CS partially in their genetic, somatic, and neuropathologic features. Mutations of CSA or CSB genes jeopardize transcription-coupled repair of damaged nuclear and mitochondrial DNA and resumption of replication and transcription. Resultant defective proteins or gene silencing eventuate in profound dwarfism and micrencephaly, cachexia, vasculopathy, and neurodegeneration. Cellular effects are highly selective. Purkinje cells may die by apoptosis and have grossly dystrophic dendrites. Neuronal death and axonal spheroids indexing neuronal pathology predominate in, but are not limited to, the cerebellum. Progressive loss of retinal, cochlear, and vestibular sensory receptors foster degeneration of ganglion cells and transneuronal brain degeneration. Some proliferating astrocytes are multinucleated and bizarre. Primary damage of oligodendrocytes and Schwann cells may - or may not - explain severe patchy myelin loss ("tigroid leukodystrophy") and segmental demyelinating peripheral neuropathy. Age-related changes are minor in the brain, although precocious severe athero- and arteriolosclerosis are responsible for occasional strokes. Vasculopathology may contribute to myelin loss and to dystrophic mineralization of neurons and vessels, especially in basal ganglia and cerebellum. Understanding the genetics, biochemical, and cellular pathophysiology of these disorders remains fragmentary.

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Crossref · 10.1016/j.mad.2009.07.006

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  • Conditions with mutations in NER pathways include xeroderma pigmentosum (XP), Cockayne syndrome (CS), trichothiodystrophy (TTD), UV-sensitive syndrome (UV-SS), and cerebro-oculo-facioskeletal syndrome (COFS).

    “These include the conditions with mutations in NER pathways (presented in Table 3) such as xeroderma pigmentosum (XP) [149,150], Cockayne syndrome (CS) [151,152], trichothiodystrophy (TTD) [153,154,155,156], UV-sensitive syndrome (UV-SS), and cerebro-oculo-facioskeletal syndrome (COFS) [157,158,159].”

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Authors
Weidenheim, K. M., Dickson, D. W., & Rapin, I.
Affiliations
Albert Einstein College of Medicine (US)
Corresponding author
Rapin, Isabelle
Venue
Mechanisms of Ageing and Development
Publisher
Elsevier BV
Published
2009-09
Volume
130
Issue
9
Pages
619-636
ISSN
0047-6374 (ISSN-L)
OpenAlex
W2041742383
Cited by
156
References
108
Citations by year
2026: 7 · 2025: 5 · 2024: 7 · 2023: 2 · 2022: 9 · 2021: 12 · 2020: 10 · 2019: 5 · 2018: 8 · 2017: 7 · 2016: 14 · 2015: 9 · 2014: 15 · 2013: 12 · 2012: 15
FWCI
4.12
Type
journal article
Language
en
Open access
closed
Locations
  • Mechanisms of Ageing and Development (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Keywords
Cockayne syndrome, xeroderma pigmentosum, transcription-coupled repair, premature aging, neurodegeneration, cerebellar degeneration, demyelinating peripheral neuropathy, vasculopathy, oligodendrocyte damage, Schwann cells, development failure, dwarfism, microcephaly, gene silencing
MeSH terms
Adolescent, Adult, Child, Cockayne Syndrome, Female, Humans, Male, Myelin Sheath, Nerve Degeneration, Neurons, Physiological Phenomena, Fatal Outcome, Aging, Premature

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