title: Cockayne syndrome: clinicopathologic and tissue culture studies of affected siblings.
abstract: Two siblings with Cockayne syndrome (CS) had extremely severe and early onset cachectic dwarfism, developmental delay, cataracts, microcephaly, peripheral neuropathy, and spastic quadriplegia. In order to study the inherited DNA-repair defect known to be present in cultured CS cells, a lymphoblastoid line was established from the younger sibling. Tissue culture studies revealed the line to have a hypersensitivity to the lethal effects of 254-nm ultraviolet radiation (UV) equivalent to that of lymphoblastoid lines from CS patients who had either the usual severity or a very mild form of CS. Autopsy of the older sibling at six years of age showed the brain to be severely atrophic, with particularly severe cerebellar atrophy. There was a marked reduction in the number of granule cells in the cerebellum and irregular patchy myelination throughout the brain. Many astrocytes contained either a large, bizarre-shaped nucleus or multiple nuclei. Some Purkinje cells of the cerebellum and pyramidal neurons of the hippocampus were binucleated. It is suggested that the DNA-repair defect of CS causes abnormalities in nuclear DNA replication and cell division which result in cell death and in the observed nuclear abnormalities.
mesh_terms: D001921:Brain / Q000473:pathology; D002470:Cell Survival / Q000528:radiation effects; D002648:Child; D003057:Cockayne Syndrome / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D046508:Culture Techniques; D004392:Dwarfism / Q000473:pathology*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects; D008297:Male; D009420:Nervous System / Q000473:pathology; D014466:Ultraviolet Rays