Ashkenazi Jewish population frequency of the Bloom syndrome gene 2281Δ6ins7 mutation

Benjamin B. Roa, Carlo V. Savino, Carolyn (Sue) Richards

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)219-221
Number of pages3
JournalGenetic Testing
Volume3
Issue number2
StatePublished - 1999
Externally publishedYes

Fingerprint

Bloom Syndrome
Mutation
Population
Genes
RecQ Helicases
Alleles
DNA Helicases
Founder Effect
Chromosome Breakage
Frameshift Mutation
Sister Chromatid Exchange
Genomic Instability
Solar System
Erythema
Heterozygote
Oligonucleotides
Molecular Biology
Nucleotides
Chromosomes
DNA

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Ashkenazi Jewish population frequency of the Bloom syndrome gene 2281Δ6ins7 mutation. / Roa, Benjamin B.; Savino, Carlo V.; Richards, Carolyn (Sue).

In: Genetic Testing, Vol. 3, No. 2, 1999, p. 219-221.

Research output: Contribution to journalArticle

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