title: Cockayne syndrome: Clinical features, model systems and pathways.
abstract: Cockayne syndrome (CS) is a disorder characterized by a variety of clinical features including cachectic dwarfism, severe neurological manifestations including microcephaly and cognitive deficits, pigmentary retinopathy, cataracts, sensorineural deafness, and ambulatory and feeding difficulties, leading to death by 12 years of age on average. It is an autosomal recessive disorder, with a prevalence of approximately 2.5 per million. There are several phenotypes (1-3) and two complementation groups (CSA and CSB), and CS overlaps with xeroderma pigmentosum (XP). It has been considered a progeria, and many of the clinical features resemble accelerated aging. As such, the study of CS affords an opportunity to better understand the underlying mechanisms of aging. The molecular basis of CS has traditionally been ascribed to defects in transcription and transcription-coupled nucleotide excision repair (TC-NER). However, recent work suggests that defects in base excision DNA repair and mitochondrial functions may also play key roles. This opens up the possibility for molecular interventions in CS, and by extrapolation, possibly in aging.
authors: Clinical Research Branch, National Institute on Aging, Baltimore, MD, USA.
authors: Ajoy C
authors: AC
authors: Karikkineth
authors: Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD, USA; Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
authors: Morten
authors: M
authors: Scheibye-Knudsen
authors: Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD, USA.
authors: Elayne
authors: E
authors: Fivenson
authors: Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD, USA.
authors: Deborah L
authors: DL
authors: Croteau
authors: Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD, USA. Electronic address: vbohr@nih.gov.
authors: Vilhelm A
authors: VA
authors: Bohr
mesh_terms: D000375:Aging / Q000502:physiology*; D019588:Aging, Premature / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D003057:Cockayne Syndrome / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D003071:Cognition; D004260:DNA Repair / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D008954:Models, Biological; D063189:Symptom Assessment / Q000379:methods; D015533:Transcriptional Activation
keywords: Cockayne syndrome; Mitochondria; Neurodegeneration; Parylation; Progeria; Transcription