Novel splice site mutation at IVS8 nt 5 of HEXB responsible for a Greek-Cypriot case of Sandhoff disease
✍ Scribed by Kenichi Furihata; Anthi Drousiotou; Yoji Hara; George Christopoulos; Goula Stylianidou; Violetta Anastasiadou; Ichiro Ueno; Panos Ioannou
- Book ID
- 101260344
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 442 KB
- Volume
- 13
- Category
- Article
- ISSN
- 1059-7794
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✦ Synopsis
Sandhoff disease is caused by abnormalities in HEXB gene encoding the b-subunit of b-hexosaminidase. In this study, we analyzed the HEXB gene of a Sandhoff carrier in the Greek-Cypriot community. A G to C transversion was identified in one allele of her HEXB gene at position 5 of the 5¢-splice site of intron 8 (IVS8 nt5). One of 13 cDNA clones derived from her lymphocyte HEXB mRNA lacked the last four nucleotides GTTG of exon 8, which created a premature termination codon at 11 codons downstream. In vivo transcription of the mutant HEXB gene fragment in CHO cells resulted in deletion of the GTTG. The mutation has not been found in 40 DNA samples from anonymous donors, indicating that this is not a polymorphism in the Cypriot population. These results clearly indicate that the splice site mutation at IVS8 nt5 is responsible for this case of Sandhoff disease.