Bloom's Syndrome: Clinical Spectrum, Molecular Pathogenesis, and Cancer Predisposition

2016/11/04 by Christopher Cunniff, Jennifer A. Bassetti, Nathan A. Ellis · 2 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #DNA Repair Mechanisms #Genomics and Chromatin Dynamics #CRISPR and Genetic Engineering #Bloom syndrome #Genetics #Frameshift mutation #Germline mutation #Chromosome instability #Nonsense mutation #Missense mutation #Cancer #Cancer syndrome #Biology #Medicine #Mutation #Chromosome #Gene #Helicase

paper · pdf · doi:10.1159/000452082

openalex publication_date 2016/11/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

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 of BLM, 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 designated blmAsh is 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.

Citations

• Bloom's syndrome. XX. The first 100 cancers
• Carrier Frequency of the Bloom SyndromeblmAshMutation in the Ashkenazi Jewish Population
• Evaluation of Short Stature, Carbohydrate Metabolism and Other Endocrinopathies in Bloom’s Syndrome
• Back mutation can produce phenotype reversion in Bloom syndrome somatic cells
• Functional Interaction of p53 and BLM DNA Helicase in Apoptosis
• Growth deficiency and malnutrition in Bloom syndrome
• Exome Sequencing Identifies Rare Deleterious Mutations in DNA Repair Genes FANCC and BLM as Potential Breast Cancer Susceptibility Alleles
• Syndrome-causing mutations of theBLMgene in persons in the Bloom's Syndrome Registry
• PML Nuclear Bodies

Cited by

• Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges
• Bloom syndrome [wikipedia]

Related

• Syndrome-causing mutations of theBLMgene in persons in the Bloom's Syndrome Registry
• Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome
• Mechanism of Bloom syndrome complex assembly required for double Holliday junction dissolution and genome stability
• Mutations in TOP3A Cause a Bloom Syndrome-like Disorder
• Exome Sequencing Identifies Rare Deleterious Mutations in DNA Repair Genes FANCC and BLM as Potential Breast Cancer Susceptibility Alleles