- databases for immunodeficiency-causing variations

   Variation registry for  Bloom syndrome

Recent results from the analysis of BLMbase

Jouni Väliaho and Mauno Vihinen

The latest publication on Molecular Medicine 2000; 6:(3)155-164
Structural Basis of Bloom Syndrome (BS) Causing Mutations in the BLM Helicase Domain
Suo-Bao Rong, Jouni Väliaho, and Mauno Vihinen
Full text as HTML and as PDF format.
Figures:Figure 1 Figure 2A Figure 2BFigure 3

Bloom syndrome (BS) is a rare human autosomal recessive disorder cased by mutations in the gene (BLM) coding for Bloom syndrome protein. Patient with BS have growth retardation, immunodeficiency and increased risk of malignancy at an early age. Hereditary immunodeficiency-causing mutations are collected into ImmunoDeficiency mutatation databases (IDbases) (1), which are available at IDbases contain mutation data, both published and directly submitted information. For each patient the following information is given (when available): The identification of the entry and plain English description of the mutation are followed by reference and formal characterisation of the mutation. Last are the various parameters from the patient.

IDbases are maintained with MUTbase program suite (2) which provides an easy, interactive and quality controlled submission of information to mutation databases. For further study of the databases on the World Wide Web, a number of tools are provided. The program package also writes and updates a large number of Web pages e.g. about distribution and statistics of disease-causing mutations, and changes in restriction patterns.

BLM protein comprises of 1417 amino acids. It belongs to the RecQ subfamily of helicases. It consists of seven distinct structural domains, which are from the N-terminus, poly-aspartate domain (PD1), poly-serine domain (PS), poly-aspartate domain (PD2), DEAH helicase domain (DEAH), RecQ helicase C-terminal domain (RecQCt), helicase and RNase D C-terminal domain (HRDC). The structural consequences of mutations in DEAH domain have been studied based on computer-aided molecular modeling.

BLMbase ( (3) lists 33 mutation entries from 32 unrelated families showing 23 unique molecular events. The most common mutation is delATCTGA/insTAGATTC at position 2281 known as blmAsh mutation (4). The carrier frequency to this mutation is about 1/104 in the Ashkenazi Jewish population. The numbers of individual mutation types for unique molecular events are 7 missense mutations, 8 nonsense mutations, 3 frameshift insertions and 5 frameshift deletions. All missense mutations are in the highly conserved DEAH or RecQ C-terminal helicase domains.


  1. Vihinen, M., Arredondo-Vega, F. X., Casanova, J. L., Etzioni, A., Giliani, S., Hammarström, L., Hershfield, M. S., Heyworth, P. G., Hsu, A. P., Lähdesmäki, A., Lappalainen, I., Notarangelo, L. D., Puck, J. M., Reith, W., Roos, D., Schumacher, R. F., Schwarz, K., Vezzoni, P., Villa, A., Väliaho, J. and Smith, C. I. (2001) Primary immunodeficiency mutation databases. Adv Genet, 43, 103-188 [PUBMED Abstract].
  2. Riikonen, P. and Vihinen, M. (1999) Bioinformatics, 15, 852-859 [PUBMED Abstract].
  3. Rong, S. B., Väliaho, J. and Vihinen, M. (2000) Structural basis of Bloom syndrome (BS) causing mutations in the BLM helicase domain. Mol Med, 6, 155-164 [PUBMED Abstract].
  4. German, J. (1999) The immunodeficiency of Bloom Syndrome. In Ochs, H. D. (ed.), Primary Immunodeficiency Diseases. A Molecular and Genetic Approach. Oxford University Press, New York, Oxford, pp. 335-338.

This site is updated by Jouni Väliaho.
Last modified