ORPHA: 178338; DO: 0060240;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q12.1 | UV-sensitive syndrome 2 | 614621 | Autosomal recessive | 3 | ERCC8 | 609412 |
A number sign (#) is used with this entry because of evidence that UV-sensitive syndrome-2 (UVSS2) is caused by homozygous mutation in the ERCC8 gene (609412) on chromosome 5q12.
UV-sensitive syndrome-2 (UVSS2) is an autosomal recessive disorder characterized by cutaneous photosensitivity and increased freckling, without an increased risk of skin tumors. Patient cells show impaired recovery of RNA synthesis (RRS) after UV irradiation due to defective preferential repair of DNA damage in actively transcribing genes, although unscheduled DNA repair is normal. The cellular findings are consistent with a defect in transcription-coupled nucleotide excision repair (TC-NER) of UV damage (summary by Nardo et al., 2009).
See also Cockayne syndrome type A (CSA; 216400), an allelic disorder with a more severe phenotype including neurologic symptoms and skeletal abnormalities.
For a general phenotypic description and a discussion of genetic heterogeneity of UVSS, see UVSS1 (600630).
Nardo et al. (2009) reported a 15-year-old French girl with UV-sensitive syndrome. She presented at age 4 months with sun sensitivity manifest as easy sun burning and erythema. She had numerous freckles on her face and exposed areas of the neck, but no history or evidence of cutaneous tumors. Psychomotor development was normal. Patient-derived fibroblasts showed a reduced recovery of RNA synthesis after UV irradiation and a defective capacity to repair UV-induced damage on the transcribed strand of active genes, indicating a defect in transcription-coupled nucleotide excision repair (TC-NER). However, there was no hypersensitivity to reactive oxygen species, and UV-induced DNA repair synthesis and global genome NER (GG-NER) were normal.
The transmission pattern of UVSS2 in the patient reported by Nardo et al. (2009) was consistent with autosomal recessive inheritance.
In a girl with UVSS2, Nardo et al. (2009) identified a homozygous mutation in the ERCC8 gene (W361C; 609412.0006). Nardo et al. (2009) hypothesized that the mild phenotype in this patient was due to the lack of cellular sensitivity to oxidative stress.
Nardo, T., Oneda, R., Spivak, G., Vaz, B., Mortier, L., Thomas, P., Orioli, D., Laugel, V., Stary, A., Hanawalt, P. C., Sarasin, A., Stefanini, M. A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage. Proc. Nat. Acad. Sci. 106: 6209-6214, 2009. [PubMed: 19329487] [Full Text: https://doi.org/10.1073/pnas.0902113106]