Journal Article

Characterization of a New <i>BLM</i> Mutation Associated with a Topoisomerase Ilα Defect in a Patient with Bloom's Syndrome

Frédéric Foucault, Christelle Vaury, Abdelhamid Barakat, Déborah Thibout, Philippe Planchon, Christian Jaulin, Françoise Praz and Mounira Amor-Guéret

in Human Molecular Genetics

Volume 6, issue 9, pages 1427-1434
Published in print September 1997 | ISSN: 0964-6906
Published online September 1997 | e-ISSN: 1460-2083 | DOI:
Characterization of a New BLM Mutation Associated with a Topoisomerase Ilα Defect in a Patient with Bloom's Syndrome

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Bloom's syndrome (BS), a human recessive disorder associated with an increased risk of malignancy, arises through mutations in both alleles of the BLM gene, which was recently identified as a member of the RecQ helicase family. BS cells are characterized by an increased rate of sister chromatid exchange (SCE). However, a subpopulation of lymphocytes exhibiting a normal level of SCE is observed in some patients. It has been proposed that reversion to a low-SCE phenotype involves an intragenic crossing over between the paternal and maternal BLM alleles, generating a wild-type allele. In this study we characterize a new BLM mutation in a BS patient leading to the replacement, in the C-terminal region of Blm, of a highly conserved cysteine by a phenylalanine in codon 1036. Moreover, our data show that this patient also inherited a BLM allele carrying a mutation affecting its expression and that a somatic intragenic crossing over was involved in reversion to the low-SCE phenotype. Further, we show that both topoisomerase llα mRNA and protein levels are decreased in the high-SCE cells derived from this patient, whereas they are normal in the corresponding low-SCE cells. Altogether, our data led us to propose that besides its putative helicase activity, Blm could be involved in transcription regulation.

Journal Article.  5914 words.  Illustrated.

Subjects: Genetics and Genomics

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