WRN

About WRN

WRN on chromosome 8p12 encodes Werner syndrome protein, a member of the RecQ family of DNA helicases that also has exonuclease activity. It helps unwind unusual DNA structures and participates in DNA replication, repair of double strand breaks, and telomere maintenance. Variants on both copies cause Werner syndrome, an autosomal recessive adult progeroid syndrome in which signs of premature aging begin in adolescence or early adulthood, often first noticed as absence of the pubertal growth spurt. Features include early graying and loss of hair, thin and tight skin, skin ulcers, bilateral cataracts, type 2 diabetes, osteoporosis, hypogonadism, atherosclerosis, and an increased risk of cancers, particularly sarcomas and other non epithelial tumors. Lifespan is shortened, with death typically in middle age from cardiovascular disease or cancer. The condition was described by the German physician Otto Werner in 1904, and the gene was identified in 1996. It is rare worldwide but relatively more common in Japan, where founder variants occur. Unlike Hutchinson Gilford progeria, caused by LMNA variants and beginning in early childhood, Werner syndrome appears in adulthood. WRN has also emerged as a synthetic lethal target in cancers with microsatellite instability, and WRN helicase inhibitors are in clinical trials.