A third mutation at the CpG dinucleotide of codon 504 and a silent mutation at codon 506 of the HEX A gene.

作者: B H Paw , E F Neufeld , L C Wood

DOI:

关键词: Silent mutationCompound heterozygosityGeneTransition (genetics)MutationGangliosidosisGeneticsCpG siteMolecular biologyMutagenesisBiology

摘要: Abstract Two CpG mutations at codon 504 of the gene encoding alpha-subunit beta-hexosaminidase (the HEX A gene) have been identified previously: (1) a C deletion resulting in premature termination and (2) G----A transition 504Arg----His substitution, patients with infantile Tay-Sachs disease juvenile GM2 gangliosidosis, respectively. This prompted search for C----T same dinucleotide, as would be expected from mechanism mutagenesis. Such mutation, which results substitution cysteine arginine, was found patient chronic compound heterozygosity known 269Gly----Ser allele. The biochemical phenotype 504Arg----Cys mutation examined by site-directed mutagenesis cDNA transfection Cos-1 cells. expression mutagenized gave rise to an defects those histidine substitution--i.e., secretion primarily alpha-monomer rather than alpha dimer, along absence enzymatic activity. 504Arg----Cys/269Gly----Ser genotype gangliosidosis is shared her sibling, who has mild adult-onset implying that clinical differences between them must attributed other factors. family unique yet another respect--namely, normal allele mother heterozygous sibling silent wobble position glutamic acid 506.(ABSTRACT TRUNCATED AT 250 WORDS)

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