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

@entity1 @entity1051 @entity377 @entity12744
We report the sixth mutation associated with the infantile form of @entity1051 in the Turkish population. The mutation is a single @entity377 transition (G to A) at the last @entity377 of exon 3 of @entity12744 ( @entity12744 ) alpha-subunit gene. The 14 exons and their flanking sequences of the @entity12744 gene were amplified and analyzed by polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP). Sequencing of exon 3 showed a homozygous mutation. Cultured @entity1 's fibroblasts produced no detectable mRNA for @entity12744 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 @entity1051 is associated with a total lack of @entity12744 activity in the @entity1 . 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 @entity12744 gene ablate normal mRNA splicing. Identification of multiple mutant @entity12744 alleles shows molecular heterogeneity of infantile @entity1051 in our population.
