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Novel HEXA mutation in a Bedouin Tay-Sachs patient associated with exon skipping and reduced transcript level

✍ Scribed by Liat Drucker; Agi Golan; Debra J. Boles; Khalil El Bedour; Richard L. Proia; Ruth Navon


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
145 KB
Volume
9
Category
Article
ISSN
1059-7794

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✦ Synopsis


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 17bp 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.