The deletion of the transcription factor 4 gene suggested a possible contribution of the deletion to the patient's facial abnormalities, as observed in Pitt-Hopkins syndrome. Together with other reported cases with interstitial deletion of 18q, a possible contribution of haploinsufficiency in both MBD1 and MBD2 genes to a Rett syndrome-like phenotype was suggested, but further genetic studies on other cases are necessary to clarify the genotype-phenotype correlation.

Bloom's syndrome (BS) is a rare autosomal recessive disorder characterized by stunted growth, sun-sensitive erythema and immunodeficiency. Chromosomal abnormalities are often observed. Patients with BS are highly predisposed to cancers. The causative gene for BS has been identified as BLM. The former encodes a protein, which is a homologue of the RecQ DNA helicase family, a family which includes helicases such as Esherichia coli RecQ, yeast Sgs1, and human WRN. WRN is encoded by the gene that when mutated causes Werner's syndrome. The function of BLM in DNA replication and repair has not yet been determined, however. To understand the function of BLM in haematopoietic cells and the cause of immunodeficiency in BS, expression of the BLM gene in various human tissues and haematopoietic cell lines was analysed and the involvement of BLM in immunoglobulin rearrangement examined. In contrast to WRN, BLM was expressed strongly in the testis and thymus. B, T, myelomonocytic and megakaryocytic cell lines also expressed BLM. All of the examined sequences at the junction of the variable (V), diversity (D) and joining (J) regions of the immunoglobulin heavy-chain genes were in-frame, and N-region insertions were also present. The frequency of abnormal rearrangements of the T cell receptor was slightly elevated in the peripheral T cells of patients with BS compared with healthy individuals, whereas a higher frequency of abnormal rearrangements was observed in the cells of patients with ataxia-telangiectasia (A-T). In DND39 cell lines, the induction of sterile transcription, which is required for class switching of immunoglobulin heavy-chain constant genes, was correlated with the induction of the BLM gene. Taking into consideration all these results, BLM may not be directly involved in VDJ recombination, but is apparently involved in the maintenance of the stability of DNA.

No abstract

Bloom syndrome (BS) is characterized by premature aging and high predisposition to various types of cancer. BLM is the causative gene for BS. BLM functions as a DNA helicase in the direction of 3' to 5' and small subsets of telomeres colocalize with BLM protein. We investigated telomerase activity and telomere repeat length in the cells from BS patients. In Epstein-Barr-virus (EBV) transformed lymphoblastoid cell lines and lymphoma cells from BS patients, telomerase activity was detected as in the control and compared. The metastatic tumor from BS patient, which had a 9-bp deletion of p53 DNA showed the strongest telomerase activity. Telomere repeat length in BS cells showed that there is no large difference compared with normal cells. Collectively, the results show that the BLM gene is not a major structural and regulatory factor in maintaining telomere repeat length and telomerase activity.