DNA helicases function in DNA replication and DNA repair. BLM very likely functions in DNA replication, as cells from persons with Bloom syndrome exhibit multiple defects in DNA replication, and they are sensitive to agents that obstruct DNA replication.The BLM helicase is a member of a protein complex with topoisomerase III alpha, RMI1 and RMI2, also known as BTRR, Bloom Syndrome complex or the dissolvasome. Disruption of the proper assembly of the Bloom Syndrome complex leads to genome stability, genetic dependence on cellular nucleases GEN1 and MUS81, and loss of normal cell growth. Bloom-like phenotypes have been associated with mutations in topoisomerase III alpha, RMI1 and RMI2 genes. Relationship to cancer and aging
As noted above, there is greatly elevated rate of mutation in Bloom syndrome and the genomic instability is associated with a high risk of cancer in affected individuals. The cancer predisposition is characterized by 1) broad spectrum, including leukemias, lymphomas, and carcinomas, 2) early age of onset relative to the same cancer in the general population, and 3) multiplicity, that is, synchronous or metachronous cancers. There is at least one person with Bloom syndrome who had five independent primary cancers. Persons with Bloom syndrome may develop cancer at any age. The average age of cancer diagnoses in the cohort is approximately 26 years old. Pathophysiology
When a cell prepares to divide to form two cells, the chromosomes are duplicated so that each new cell will get a complete set of chromosomes. The duplication process is called DNA replication.
Despite these reductions, several women with Bloom syndrome have had children, and there is a single report of a male with Bloom syndrome bearing children.Although some persons with Bloom syndrome can struggle in school with subjects that require abstract thought, there is no evidence that intellectual disability is more common in Bloom syndrome than in other people.The most serious and frequent complication of Bloom syndrome is cancer. In the 281 persons followed by the Bloom Syndrome Registry, 145 persons (51.6%) have been diagnosed with a malignant neoplasm, and there have been 227 malignancies. The types of cancer and the anatomic sites at which they develop resemble the cancers that affect persons in the general population. The age of diagnosis for these cancers is earlier than for the same cancer in normal persons. And many persons with Bloom syndrome have been diagnosed with multiple cancers. The average life span is approximately 27 years. The most common cause of death in Bloom syndrome is from cancer. Other complications of the disorder include chronic obstructive lung disease and type 2 diabetes.There are a variety of excellent sources for more detailed clinical information about Bloom syndrome.There is a closely related entity that is now referred to as Bloom-syndrome-like disorder (BSLD) which is caused by mutations in components of the same protein complex to which the BLM gene product belongs, including TOP3A, which encodes the type I topoisomerase, topoisomerase 3 alpha, RMI1, and RMI2.