title: Novel splice site mutation at IVS8 nt 5 of HEXB responsible for a Greek-Cypriot case of Sandhoff disease.
abstract: Sandhoff disease is caused by abnormalities in HEXB gene encoding the beta-subunit of beta-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.
authors.affiliation: Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan. furihata@scripps.edu
authors.forename: K
authors.initials: K
authors.lastname: Furihata
authors.forename: A
authors.initials: A
authors.lastname: Drousiotou
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
authors.forename: G
authors.initials: G
authors.lastname: Christopoulos
authors.forename: G
authors.initials: G
authors.lastname: Stylianidou
authors.forename: V
authors.initials: V
authors.lastname: Anastasiadou
authors.forename: I
authors.initials: I
authors.lastname: Ueno
authors.forename: P
authors.initials: P
authors.lastname: Ioannou
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D002648:Child; D003535:Cyprus / Q000208:ethnology; D003596:Cytosine; D004268:DNA-Binding Proteins; D006151:Guanosine; D006579:Heterozygote; D054819:Hexosaminidase B; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D012326:RNA Splicing / Q000235:genetics*; D012497:Sandhoff Disease / Q000235:genetics*; D054821:beta-Hexosaminidase beta Chain; D001619:beta-N-Acetylhexosaminidases
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D006151:Guanosine; D003596:Cytosine; C513386:HEXB protein, human; D054819:Hexosaminidase B; D054821:beta-Hexosaminidase beta Chain; D001619:beta-N-Acetylhexosaminidases