NIH Research Festival
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of impaired DNA repair with features of premature aging. XP patients develop freckle-like pigmented lesions in sun exposed areas. XP patients have a 2,000- and 10,000-fold increase in melanoma and non-melanoma skin cancer, respectively. About 25% of the XP patients develop severe progressive neurologic degeneration including hearing loss. In analyzing our 40 yr follow-up study of 56 post-pubertal women with XP, we found that 10 of 13 menopausal women had experienced cessation of menses before 40 years of age. The median age of XP women at menopause (30.0 yr) was 23 yr younger than in the general population (52.9 yr). Of the 10 women with premature menopause, 9 were known to have mutations in the XPC gene. These results suggest that human ovaries sustain DNA damage and DNA repair plays a role in maintenance of normal ovarian function. In addition, 3 male XP-C patients developed new hematologic neoplasms: one developed myelodysplastic syndrome (MDS) and died at age 20 yr following a bone marrow transplant; an African patient died at age 29 yr with a rapidly progressive B cell lymphoma; and one died at age 39 yr from myeloid leukemia with MDS. MDS is rare under age 40 years and typically occurs after age 60. With better sun protection, early skin cancer detection and treatment, more XP patients are surviving into adulthood. These XP patients are developing previously unrecognized features of premature aging, including premature menopause and hematologic neoplasms.
Scientific Focus Area: Genetics and Genomics
This page was last updated on Friday, March 26, 2021