1/2. xeroderma pigmentosum/cockayne syndrome complex: first neuropathological study and review of eight other cases.This is the first detailed description of the neuropathology of a patient with xeroderma pigmentosum/cockayne syndrome complex (XP/CS). This 6-year-old boy's clinical course, followed from infancy to death, is compared with that of the eight other known cases of XP/CS. Normal at birth, he developed the cutaneous sun sensitivity of XP in infancy and the infantile CS phenotype in early childhood. He had the characteristic CS facies, cachexia, failure of somatic and brain growth, spasticity, ataxia, pigmentary retinopathy, hearing loss, mixed peripheral neuropathy, and myopathy. Like his clinical phenotype, the neuropathology was also that of CS despite an XPG genotype. His brain weighed 350 grams (considerably less than the expected weight at birth) and revealed hydrocephalus, tigroid-type demyelination, dystrophic calcification and widespread neuronal loss and gliosis with hyperchromatic glial and endothelial nuclei. Peripheral nerve showed myelinopathy with axonal degeneration, and skeletal muscle had mixed myopathic and neuropathic features. Ophthalmic pathology disclosed cataracts, iris and ciliary body atrophy, inner retinal atrophy and gliosis, retinal pigment epithelial atrophy, and optic nerve atrophy. Molecular studies, which have appeared elsewhere, do not provide full understanding of the pathophysiology of the postnatal growth failure, cachexia, precocious aging, selectivity of tissues affected (such as myelinated axons), and other manifestations of this devastating illness.- - - - - - - - - - ranking = 1keywords = cockayne syndrome, cockayne (Clic here for more details about this article) |
2/2. dna repair and ultraviolet mutagenesis in cells from a new patient with xeroderma pigmentosum group G and cockayne syndrome resemble xeroderma pigmentosum cells.xeroderma pigmentosum (XP)/cockayne syndrome (CS) complex is a combination of clinical features of two rare genetic disorders in one individual. A sun-sensitive boy (XP20BE) who had severe symptoms of CS, with dwarfism, microcephaly, retinal degeneration, and mental impairment, had XP-type pigmentation and died at 6 y with marked cachexia (weight 14.5 lb) without skin cancers. We evaluated his cultured cells for characteristic CS or XP DNA-repair abnormalities. The level of ultraviolet (UV)-induced unscheduled DNA synthesis was less than 5% of normal, characteristic of the excision-repair defect of XP. cell fusion studies indicated that his cells were in XP complementation group G. His cells were hypersensitive to killing by UV, and their post-UV recovery of rna synthesis was abnormally low, features of both CS and XP. Post-UV survival of plasmid pSP189 in his cells was markedly reduced, and post-UV plasmid mutation frequency was higher than with normal cells, as in both CS and XP. sequence analysis of the mutated plasmid marker gene showed normal frequency of plasmids with multiple base substitutions, as in CS, and an abnormally increased frequency of G:C-->A:T mutations, a feature of XP. transfection of UV-treated pRSVcat with or without photoreactivation revealed that his cells, like XP cells, could not repair either cyclobutane pyrimidine dimers or non-dimer photoproducts. These results indicate that the DNA-repair features of the XP20BE (XP-G/CS) cells are phenotypically more like XP cells than CS cells, whereas clinically the CS phenotype is more prominent than XP.- - - - - - - - - - ranking = 1keywords = cockayne syndrome, cockayne (Clic here for more details about this article) |