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Bloom syndrome

Author
Andrew Gennery, MD
Section Editor
E Richard Stiehm, MD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

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 [1].

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".)

EPIDEMIOLOGY

Bloom syndrome (BS) is a rare disorder, with 272 cases reported in the Bloom's Syndrome Registry through 2012 [2]. 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.

PATHOGENESIS

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 [10]. 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].

CLINICAL MANIFESTATIONS

Bloom syndrome (BS) is characterized by [2,7,8,20,21]:

       

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Literature review current through: Nov 2016. | This topic last updated: Wed Jul 15 00:00:00 GMT 2015.
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References
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