Mutations of the hexosaminidase A gene in Ashkenazi and non-Ashkenazi Jews

Biochem Med Metab Biol. 1994 Jun;52(1):22-6. doi: 10.1006/bmmb.1994.1029.


Tay-Sachs disease (TSD) is caused by mutations in the gene encoding the alpha-subunit of beta-hexosaminidase A (HexA). This disease is more prevalent in certain ethnic groups such as Jews of Ashkenazi origin. Three mutations are most commonly found among the latter population: a 4-nucleotide insertion in exon 11, a transversion at the splice site in intron 12, and the adult onset mutation in exon 7. The frequency and distribution of these mutations among Ashkenazi and non-Ashkenazi Jews were examined: 96% of the Ashkenazi carriers bore one of these mutations, while in only 30% of the non-Ashkenazi Jewish carriers were the mutations identified. The percentage distribution of the exon 11:intron 12:exon 7 and unidentified mutant allele(s) was 82:10:4:4 among 152 Ashkenazi carriers, and 16:12:2:70 among non-Ashkenazi Jewish carriers. When the non-Ashkenazi Jewish population was divided into two groups according to the geographical distance from Eastern Europe, it was obvious that the ancestral origin of the subjects bearing the exon 11 allele was predominantly from countries bordering Eastern and Central Europe, such as Turkey, Bulgaria, and Georgia. In carriers from other geographical areas of North Africa and the Middle East, this allele was about fivefold less frequent. The result is compatible with the assumption that this gene, of which the tested individuals were unaware, originates from interethnic marriage in neighboring populations. However, regardless of the ancestral origin, the intron 12 allele was quite evenly distributed throughout the Jewish population.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Alleles
  • DNA / analysis
  • Exons / genetics
  • False Negative Reactions
  • Heterozygote
  • Hexosaminidase A
  • Humans
  • Introns / genetics
  • Israel
  • Jews*
  • Mutation*
  • beta-N-Acetylhexosaminidases / genetics*


  • DNA
  • Hexosaminidase A
  • beta-N-Acetylhexosaminidases