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

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. Hum Mutat 9:260–264, 1997. © 1997 Wiley-Liss, Inc.