Bloom syndrome is an autosomal recessive disorder characterized clinically by small size, sun-sensitive facial erythema, and immunodeficiency, and cytogenetically by increased chromosome breakage and sister chromatid exchange. Genomic instability renders Bloom syndrome patients at elevated risk for multiple cancers. Bloom syndrome occurs most commonly in the Ashkenazi Jewish population due to an apparent founder effect. The BLM gene on chromosome 15q26.1 was identified to encode a RecQ DNA helicase. Multiple mutations were identified, with Ashkenazi Jewish Bloom syndrome patients almost exclusively homozygous for a complex frameshift mutation (6-bp deletion/7-bp insertion at BLM nucleotide 2,281). This molecular genetic study seeks to verify the Ashkenazi Jewish carrier frequency of the BLM 2281Δ6ins7 allele using semiautomated allele-specific oligonucleotide (ASO) analysis. Anonymized DNA samples from 1,016 Ashkenazi Jewish individuals and 307 non-Jewish individuals were screened. Ten Ashkenazi heterozygote carriers for the 2281Δ6ins7 mutation were identified, giving a carrier frequency estimate of 0.98%, or approximately 1 carrier out of 102 individuals in the Ashkenazi Jewish population. These results are consistent with previous estimates, and combining our findings with the published molecular data collectively yields an Ashkenazi Jewish carrier frequency of approximately 1 in 104. Given its high population frequency and detection rate among Ashkenazi Jewish patients, the blm(Ash) mutation constitutes an appropriate addition to screening panels for Ashkenazi Jewish disease testing.
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