A new point mutation (G412 to A) at the last nucleotide of exon 3 of hexosaminidase α-subunit gene affects splicing
- 作者：Ö ; zkara ; Hatice Asuman ; Sandhoff ; Konrad
- 关键词：Hexosaminidase A ; Tay-Sachs disease ; Mutation
- 刊名：Brain and Development
- 出版年：2003
- 期刊代码：40_03877604
- 类别：med
- 出版时间：April, 2003
- 卷：25
- 期：3
- 页码：203-206
- 文件大小：156 K
摘要
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) α-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 α-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.