title: Bloom's Syndrome: Clinical Spectrum, Molecular Pathogenesis, and Cancer Predisposition.
abstract: Bloom's syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early onset of cancer and for the development of multiple cancers. Loss-of-function mutations ofBLM, which codes for a RecQ helicase, cause Bloom's syndrome. The absence of a functional BLM protein causes chromosome instability, excessive homologous recombination, and a greatly increased number of sister chromatid exchanges that are pathognomonic of the syndrome. A common founder mutation designatedblmAshis present in about 1 in 100 persons of Eastern European Jewish ancestry, and there are additional recurrent founder mutations among other populations. Missense, nonsense, and frameshift mutations as well as multiexonic deletions have all been observed. Bloom's syndrome is a prototypical chromosomal instability syndrome, and the somatic mutations that occur as a result of that instability are responsible for the increased cancer risk. Although there is currently no treatment aimed at the underlying genetic abnormality, persons with Bloom's syndrome benefit from sun protection, aggressive treatment of infections, surveillance for insulin resistance, and early identification of cancer.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Weill Cornell Medical College, New York, N.Y, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cunniff
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Weill Cornell Medical College, New York, N.Y, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Bassetti
authors.affiliation: Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, Tucson, Ariz., USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Ellis
keywords: BLM; Bloom's syndrome; Cancer