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UV-sensitive syndrome (UV S S) is a recently-identified autosomal recessive disorder characterized by mild cutaneous symptoms and defective transcription-coupled repair (TC-NER), the subpathway of nucleotide excision repair (NER) that rapidly removes damage that can block progression of the transcription machinery in actively-transcribed regions of DNA. Cockayne syndrome (CS) is another genetic disorder with sun sensitivity and defective TC-NER, caused by mutations in the CSA or CSB genes. The clinical hallmarks of CS include neurological/developmental abnormalities and premature aging. UV S S is genetically heterogeneous, in that it appears in individuals with mutations in CSB or in a still-unidentified gene. We report the identification of a UV S S patient (UV S S1VI) with a novel mutation in the CSA gene (p.trp361cys) that confers hypersensitivity to UV light, but not to inducers of oxidative damage that are notably cytotoxic in cells from CS patients. The defect in UV S S1VI cells is corrected by expression of the WT CSA gene. Expression of the p.trp361cys-mutated CSA cDNA increases the resistance of cells from a CS-A patient to oxidative stress, but does not correct their UV hypersensitivity. These findings imply that some mutations in the CSA gene may interfere with the TC-NERdependent removal of UV-induced damage without affecting its role in the oxidative stress response. The differential sensitivity toward oxidative stress might explain the difference between the range and severity of symptoms in CS and the mild manifestations in UV s S patients that are limited to skin photosensitivity without precocious aging or neurodegeneration.

Hallucinations, and auditory hallucinations (AH) in particular, constitute the most typical and disabling schizophrenia symptoms. Although visual hallucinations (VH) have been largely neglected in psychiatric disorders, a recent review reported a 27% mean prevalence of VH in schizophrenia patients. The pathophysiology underlying VH in schizophrenia remains elusive. Several schizophrenia studies reported a significant effect of age on VH; therefore, we tested the hypothesis that the neurodevelopmental model of schizophrenia may explain VH occurrence. We analyzed cortex sulcation, a marker of brain development, in healthy controls (HCs) and two subgroups of carefully selected schizophrenia patients suffering from hallucinations: patients with only AH (that is, patients who never reported VH) and patients with audio-visual hallucinations (A+VH). Different cortical sulcation and left-right sulcal asymmetry were found between A+VH and AH patients, with decreased sulcation in both A+VH and AH patients in comparison with the HCs. Although a specific association between VH and neurodegenerative mechanisms, for example, in Body-Lewy Dementia or Parkinson's Disease, has previously been reported in the literature, the current study provides the first neuroimaging evidence of an association between VH and neurodevelopmental mechanisms.

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