title: A null allele frequent in non-Jewish Tay-Sachs patients.
abstract: The molecular basis of null alleles was investigated by cDNA polymerase chain reaction (PCR) in seven Tay-Sachs patients. Although mRNAs were undetectable by Northern blot, cDNA-PCR amplification allowed us to get a sufficient amount of cDNA to characterize abnormal transcripts. In two French patients (one homozygote and one compound heterozygote with a 4-bp insertion in exon 11 of the second allele) suffering an infantile form of the disease, we detected abnormal RNAs with a 17-bp insertion due to a GT to AT transition at the donor site of intron 9, resulting in the activation of a cryptic donor site in the intron. This mutation has been found in 9 out of 82 Tay-Sachs chromosomes (11%) in association with alleles responsible from different clinical courses. In the other five patients we found the 4-bp insertion in exon 11 and two nonsense mutations.
authors.affiliation: Laboratoire de Recherches en Génétique et Pathologie Moléculaires, INSERM, U. 129, CHU Cochin, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Akli
authors.forename: J
authors.initials: J
authors.lastname: Chelly
authors.forename: A
authors.initials: A
authors.lastname: Kahn
authors.forename: L
authors.initials: L
authors.lastname: Poenaru
mesh_terms: D000483:Alleles; D001483:Base Sequence; D015152:Blotting, Northern; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis; D013661:Tay-Sachs Disease / Q000235:genetics*
chemical_list: D012333:RNA, Messenger