- Andrew Gennery, MD
Andrew Gennery, MD
- Clinical Reader/Consultant
- Newcastle University
A number of human genetic disorders cause chromosomal breakage, which is characterized by genome instability that occurs in the basal state (spontaneously) or in response to DNA-damaging agents (table 1). These disorders cause defects in the recognition and/or repair of damage to DNA inflicted by different agents. In most cases, the genome instability is associated with immune deficiency, a predisposition to develop cancer, and premature aging .
This topic review will discuss Bloom syndrome (BS; MIM #210900), one of the chromosomal breakage syndromes that is associated with immunodeficiency. Discussions relating to the other disorders are presented separately. (See "Ataxia-telangiectasia" and "Nijmegen breakage syndrome".)
Bloom syndrome (BS) is a rare disorder, with 272 cases reported in the Bloom's Syndrome Registry through 2012 . The exact incidence is unknown. It has been reported in a variety of ethnic groups. However, it is more common in the Eastern European Jewish (Ashkenazi) population (approximately 25 percent of the affected families in the BS registry), with a carrier rate for the Ashkenazi mutation of approximately 1 percent and a disease prevalence of approximately 1:48,000 [3-6]. Parental consanguinity is common.
Bloom syndrome (BS; MIM #210900) is an autosomal recessive chromosomal instability disorder that is caused by mutations in the BLM gene at 15q26.1 [7-9]. This gene encodes a RecQ helicase, RECQL3, called the Bloom syndrome protein (Blm), which helps maintain the stability of DNA when the DNA duplexes are unwound during recombination repair and replication . A significant increase in gene cluster instability and sister chromatid exchange (SCE; homologous recombination associated with crossover) is seen during mitotic recombination in patients with BS [11-14]. Thus, Blm is believed to function primarily as an antirecombinase, mainly by acting as a Holliday junction dissolvase [15,16]. It also interacts with other molecules involved in the sensing and repair of DNA damage [17-19].
Bloom syndrome (BS) is characterized by [2,7,8,20,21]:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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