A new point mutation (G412 to A) at the last nucleotide of exon 3 of hexosaminidase alpha-subunit gene affects splicing

Brain Dev. 2003 Apr;25(3):203-6. doi: 10.1016/s0387-7604(02)00219-x.


We report the sixth mutation associated with the infantile form of Tay-Sachs disease in the Turkish population. The mutation is a single nucleotide transition (G to A) at the last nucleotide of exon 3 of hexosaminidase A (HEX A) alpha-subunit gene. The 14 exons and their flanking sequences of the HEX A gene were amplified and analyzed by polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP). Sequencing of exon 3 showed a homozygous mutation. Cultured patient's fibroblasts produced no detectable mRNA for HEX A alpha-subunit gene by Northern blot analysis. We speculate that abnormal mRNA was rapidly degraded following transcription. Our data are consistent with the idea that the severe infantile form of Tay-Sachs disease is associated with a total lack of Hex A activity in the patient. A similar mutation (G to T) had been observed at the 5'-donor splice site of exon 3. It resulted in abnormal splicing and skipping of exon 3. The other acceptor and donor splice site mutations described in the HEX A gene ablate normal mRNA splicing. Identification of multiple mutant HEX A alleles shows molecular heterogeneity of infantile Tay-Sachs disease in our population.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Child, Preschool
  • DNA Mutational Analysis
  • Exons / genetics
  • Female
  • Hexosaminidase A
  • Humans
  • Infant
  • Nucleotides / genetics
  • Point Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Protein Subunits / genetics
  • RNA Splice Sites / genetics
  • RNA, Messenger / analysis
  • Tay-Sachs Disease / ethnology
  • Tay-Sachs Disease / genetics*
  • Turkey / ethnology
  • beta-N-Acetylhexosaminidases / genetics*


  • Nucleotides
  • Protein Subunits
  • RNA Splice Sites
  • RNA, Messenger
  • Hexosaminidase A
  • beta-N-Acetylhexosaminidases