Expression of BLM (the causative gene for Bloom syndrome) and screening of Bloom syndrome.

Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized by growth deficiency, unusual facies, sun-sensitive telangiectatic erythema, immunodeficiency and predisposition to cancer. The causative gene for BS is the BLM gene which encodes the BLM RecQ helicase protein. The BLM gene has 4437 bp and encodes 1417 amino acids. The detection of BLM gene mutations for laboratory diagnosis of BS is laborious and impractical, unless there are common mutations in a population. Here we describe the immunoblot and immunohistochemical analyses for the detection of the BLM protein using a polyclonal BLM antibody. The BLM gene and protein were consistently and clearly detected in Epstein-Barr virus (EBV)-transformed or phytohemagglutinin (PHA)-stimulated lymphoblasts from control and various human hematopoietic cell lines. In a 7-week old human fetal brain, the BLM gene expression was strongly detected in contrast to an adult human brain. The BLM protein was not detected in EBV-transformed lymphoblasts from three BS patients. By immunohistochemistry, nuclear dots of the BLM protein were detected in both EBV-transformed lymphoblasts and PHA-stimulated lymphoblasts from the control. However, in lymphoblasts from BS patients no nuclear dots of the BLM protein were detected. These results indicate that the combinational analysis of immunoblotting and immunohistochemistry is a useful approach to screening of BS, although a mutation analysis is necessary for a definitive diagnosis of BS.