latest publication on Molecular Medicine 2000; 6:(3)155-164
Basis of Bloom Syndrome (BS) Causing Mutations in the BLM Helicase Domain
Suo-Bao Rong, Jouni Väliaho, and Mauno Vihinen
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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 http://structure.bmc.lu.se/idbase/.
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.
(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.
- 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
- Riikonen, P. and Vihinen, M. (1999) Bioinformatics, 15,
- 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
- 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.