Environmental and Molecular Mutagenesis (EMM) Editor's Choice - August 2012
The Editor's Choice for August is "A Novel XPD Mutation in a Compound Heterozygote; the Mutation in the Second Allele is Present in Three Homozygous Patients With Mild Sun Sensitivity" by Tzipora C. Falik-Zaccai, Reut Erel-Segal, Liran Horev, Ora Bitterman-Deutsch, Sivan Koka, Sara Chaim, Zohar Keren, Limor Kalfon, Bella Gross, Zvi Segal, Shlomi Orgal, Yishay Shoval, Hanoch Slor, Graciela Spivak, and Philip C. Hanawalt.
Nucleotide excision repair (NER) is a process that removes damaged bases in DNA, such as those caused by UV-light. The XPD protein is one of the proteins that comprise a large protein complex, designated transcription factor IIH, which is needed for NER. The XPD protein is a helicase that unwinds the DNA near a damaged site, thereby facilitating the repair. Inherited mutations in the XPD gene have been associated with a number of different clinical syndromes. Falik-Zaccai and colleagues characterized the XPD mutations in five patients, and showed that cells from patients with mutations in XPD were deficient in NER. The cells were unable to remove UV-light-induced DNA damage. Therefore, this work by Falik-Zaccai et al. provides important new information about how XPD mutations relate to the clinical manifestations observed in patients. One of the mutations described by Falik-Zaccai and colleagues had never been detected before. Some of the clinical features Falik-Zaccai et al. observed in patients carrying XPD mutations included: mild sun sensitivity, mild skin pigmentation, loss of tendon reflex, premature aging, late-onset skin tumors, and moderate cognitive decline. Thus, the new information provided in this study will strengthen interpretation of genetic testing for XPD mutations, and also provide guidance for the management of patients presenting with sun sensitivity. Environ. Mol. Mutagen. 53:505-514 Published 2012 Wiley Periodicals, Inc.