A novel mutation in the invariant AG of the acceptor splice site of intron 4 of the β-hexosaminidase α-subunit gene in two unrelated American black GM2-gangliosidosis (Tay-Sachs disease) patients

Emilie H. Mules, Carol E. Dowling, Michael B. Petersen, Haig Kazazian, George H. Thomas

Research output: Contribution to journalArticle

Abstract

Samples of genomic DNA from three unrelated American black infants having both biochemical and clinical features of classical infantile Tay-Sachs disease were sequenced following PCR amplification. A G → T transversion was observed in the AG acceptor splice site preceding exon 5 of the β-hexosaminidase α-subunit gene in the first black family. This transversion changed the acceptor splice site from the consensus sequence, AG, to AT, thereby interfering with splicing at this intron 4/exon 5 junction. The proband was homozygous for this mutation; his mother and a brother are heterozygous. The same mutation was found in a second, apparently unrelated, black GM2-gangliosidosis patient. The second patient was a compound heterozygote, as only one allele carried this mutation. The mother and a brother in this second family are carriers for this mutation, while the father and a noncarrier sister are normal for this region of the gene. The third proband did not have this mutation; nor did the mother of a fourth black proband. Eight other independently ascertained non-black, non-Jewish, GM2-gangliosidosis families did not have this mutation. The observation of the same novel mutation in two unrelated black GM2-gangliosidosis patients indicates that the American black population has segregating within it at least one GM2-gangliosidosis mutation which may be specific to this population and not a result of migration.

Original languageEnglish (US)
Pages (from-to)1181-1185
Number of pages5
JournalAmerican Journal of Human Genetics
Volume48
Issue number6
StatePublished - Jun 1991

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GM2 Gangliosidosis
Tay-Sachs Disease
Hexosaminidases
RNA Splice Sites
Introns
Mutation
Genes
Siblings
Mothers
Exons
Consensus Sequence
Heterozygote
Fathers
Population
Alleles
Observation

ASJC Scopus subject areas

  • Genetics

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A novel mutation in the invariant AG of the acceptor splice site of intron 4 of the β-hexosaminidase α-subunit gene in two unrelated American black GM2-gangliosidosis (Tay-Sachs disease) patients. / Mules, Emilie H.; Dowling, Carol E.; Petersen, Michael B.; Kazazian, Haig; Thomas, George H.

In: American Journal of Human Genetics, Vol. 48, No. 6, 06.1991, p. 1181-1185.

Research output: Contribution to journalArticle

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abstract = "Samples of genomic DNA from three unrelated American black infants having both biochemical and clinical features of classical infantile Tay-Sachs disease were sequenced following PCR amplification. A G → T transversion was observed in the AG acceptor splice site preceding exon 5 of the β-hexosaminidase α-subunit gene in the first black family. This transversion changed the acceptor splice site from the consensus sequence, AG, to AT, thereby interfering with splicing at this intron 4/exon 5 junction. The proband was homozygous for this mutation; his mother and a brother are heterozygous. The same mutation was found in a second, apparently unrelated, black GM2-gangliosidosis patient. The second patient was a compound heterozygote, as only one allele carried this mutation. The mother and a brother in this second family are carriers for this mutation, while the father and a noncarrier sister are normal for this region of the gene. The third proband did not have this mutation; nor did the mother of a fourth black proband. Eight other independently ascertained non-black, non-Jewish, GM2-gangliosidosis families did not have this mutation. The observation of the same novel mutation in two unrelated black GM2-gangliosidosis patients indicates that the American black population has segregating within it at least one GM2-gangliosidosis mutation which may be specific to this population and not a result of migration.",
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T1 - A novel mutation in the invariant AG of the acceptor splice site of intron 4 of the β-hexosaminidase α-subunit gene in two unrelated American black GM2-gangliosidosis (Tay-Sachs disease) patients

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AU - Thomas, George H.

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