Cellosaurus publication CLPUB00562

Publication number	CLPUB00562
Authors	Imoto K., Boyle J., Oh K.-S., Khan S.G., Ueda T., Nadem C., Slor H., Orgal S., Gadoth N., Busch D.B., Jaspers N.G.J., Tamura D., DiGiovanna J.J., Kraemer K.H.
Title	Patients with defects in the interacting nucleotide excision repair proteins ERCC1 or XPF show xeroderma pigmentosum with late onset severe neurological degeneration.
Citation	J. Invest. Dermatol. 127 Suppl. 1:S92-S92(2007)
Abstract	Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by sun sensitivity and a high incidence of skin cancer in association with defective nucleotide excision repair (NER). XP patient (XP202DC) had progressive neurodegeneration with dementia, severe generalized brain atrophy beginning at age 15 years, and death by 37 years. The ERCC1 gene in her cells had heterozygous mutations: one nonsense mutation (K226X) and one splice mutation (IVS6-26G>A). The delayed onset and severe neurological degeneration with generalized brain atrophy were very different from other XP patients but very similar to three XP patients in 2 new families (XP48DC and siblings CO14TA and CO107TA) who were heterozygous for a missense mutation (R788W) in the XPF gene. XPF and ERCC1 form a heterodimer that functions as a 5'endonuclease in a late stage of the NER reaction. XPF and ERCC1 interact in the region that is disrupted by the mutations found in our patients. The similarity of the neurologic abnormalities among the patients with ERCC1 and XP-F defects suggests that dysfunction of the XPF/ERCC1 complex causes this unusual form of severe neurological degeneration. These findings describe an important new role of NER proteins in maintaining the integrity of the central nervous system.
Cell lines	CVCL_ZP22; XP202DC