<unk>  metaphase cells exhibit frequent sister chromatid exchanges.<unk>  is an autosomal recessive disorder, caused by mutations in the maternally- and paternally-derived copies of the gene BLM. As in other autosomal recessive conditions, the parents of an individual with<unk>  do not necessarily exhibit any features of the syndrome. The mutations in BLM associated with<unk>  are nulls and missense mutations that are catalytically inactive. The cells from persons with<unk>  exhibit a striking genomic instability that is characterized by hyper-recombination and hyper-mutation. Human BLM cells are sensitive to DNA damaging agents such as UV and methyl methanesulfonate, indicating deficient repair capability. At the level of the chromosomes, the rate of sister chromatid exchange in<unk> 's syndrome is approximately 10 fold higher than normal and quadriradial figures, which are the cytologic manifestations of crossing-over between homologous chromosome, are highly elevated. Other chromosome manifestations include chromatid breaks and gaps, telomere associations, and fragmented chromosomes. The hyper-recombination can also be detected by molecular assays The BLM gene is a member of the protein family referred to as RecQ helicases. The diffusion of BLM has been measured to 1.34 in nucleoplasm and 0.13 at nucleoli DNA helicases are enzymes that attach to DNA and temporarily unravel the double helix of the DNA molecule. DNA helicases function in DNA replication and DNA repair. BLM very likely functions in DNA replication, as cells from persons with<unk>  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,<unk>  complex or the dissolvasome. Disruption of the proper assembly of the<unk>  complex leads to genome stability, genetic dependence on cellular nucleases GEN1 and MUS81, and loss of normal cell growth .<unk> -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<unk>  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<unk>  who had five independent primary cancers. Persons with<unk>  may develop cancer at any age. The average age of cancer diagnoses in the cohort is approximately 26 years old.
Bloom syndrome
Plummer–Vinson syndrome
Schnitzler syndrome
Secretan's syndrome
Galloway Mowat syndrome
Mucus fishing syndrome
Naegeli–Franceschetti–Jadassohn syndrome
König's syndrome