title: Novel HEXA mutation in a Bedouin Tay-Sachs patient associated with exon skipping and reduced transcript level.
abstract: An Israeli-Bedouin infant from a consanguineous family was diagnosed with Tay-Sachs disease (TSD). The patient was found to carry the novel +3tIVS4 mutation in homozygosity. Direct sequencing of the cDNA showed that the +3tIVS4 mutation caused complete skipping of exon 4 resulting in a stop codon 17 bp downstream. We postulate that the insertion disrupts base pairing between the consensus sequence and U1 snRNA causing exon skipping. The resultant transcript contains a premature termination codon and is severely reduced in amount. An extended nucleotide portion of the 5' end of IVS4 was sequenced.
authors.affiliation: Department of Human Genetics, Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Drucker
authors.forename: A
authors.initials: A
authors.lastname: Golan
authors.forename: D J
authors.initials: DJ
authors.lastname: Boles
authors.forename: K
authors.initials: K
authors.lastname: el Bedour
authors.forename: R L
authors.initials: RL
authors.lastname: Proia
authors.forename: R
authors.initials: R
authors.lastname: Navon
mesh_terms: D018912:Arabs; D001483:Base Sequence; D003241:Consanguinity; D004247:DNA / Q000032:analysis; D018076:DNA, Complementary / Q000032:analysis; D005091:Exons; D017809:Fatal Outcome; D054818:Hexosaminidase A; D006720:Homozygote; D006801:Humans; D007223:Infant; D007438:Introns; D007557:Israel; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D013661:Tay-Sachs Disease / Q000208:ethnology / Q000235:genetics*; D014158:Transcription, Genetic; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D012313:RNA; D004247:DNA; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases