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 language | English (US) |
|---|---|
| Pages (from-to) | 1181-1185 |
| Number of pages | 5 |
| Journal | American Journal of Human Genetics |
| Volume | 48 |
| Issue number | 6 |
| State | Published - Jun 1991 |
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ASJC Scopus subject areas
- Genetics
Cite this
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 journal › Article
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TY - JOUR
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
AU - Mules, Emilie H.
AU - Dowling, Carol E.
AU - Petersen, Michael B.
AU - Kazazian, Haig
AU - Thomas, George H.
PY - 1991/6
Y1 - 1991/6
N2 - 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.
AB - 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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M3 - Article
VL - 48
SP - 1181
EP - 1185
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 6
ER -