The Bloom syndrome (BS) is an autosomal recessive disorder associated with dwarfism, immunodeficiency, reduced fertility and cancer risk. BS cells show genomic instability, particularly an hyper exchange between the sister chromatids due to a defective processing of the DNA replication intermediates. It is caused by mutations in the BLM gene which encodes a member of the RecQ family of DExH box DNA helicases. In this study, we reported cytogenetic, BLM linkage and mutational analyses for two affected Tunisian families. The Cytogenetic parameters were performed by chromosomal aberration (CA) and sister chromatid exchange (SCE) assays and results showed a significant increase in mean frequency of CA and SCE in BS cells. BLM linkage performed by microsatellite genotyping revealed homozygous haplotypes for the BS patients, evidence of linkage to BLM gene. Mutational analysis by direct DNA sequencing revealed a novel frameshift mutation (c.1980-1982delAA) in exon 8 of BLM gene, resulting in a truncated protein (p.Lys662fsX5). The truncated protein could explain genomic instability and its related symptoms in the BS patients. The screening of this mutation is useful for BS diagnosis confirmation in Tunisian families.
© 2013 European Academy of Dermatology and Venereology.