Six novel deleterious and three neutral mutations in the gene encoding the α-subunit of hexosaminidase A in non-Jewish individuals

Emilie H. Mules, Susan Hayflick, Carol S. Miller, Linda W. Reynolds, George H. Thomas

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Initial investigations demonstrated that only 3/34 "Tay-Sachs chromosomes" in 22 unrelated, non-Jewish patients or carriers of some form of GM2-gangliosidosis (7 black and 15 non-Jewish Caucasian) had either of the two mutations commonly found in the Jewish population. To determine the nature and incidence of the alterations in this non-Jewish population we have utilized PCR, single-strand conformation polymorphism analysis and sequencing to detect new mutations in genomic DNA. Fourteen primer sets have been utilized to analyze 80% of the coding region and 23/26 splice sites of the gene coding for the alpha chain of hexosaminidase A. Presumed deleterious mutations were discovered in 17/34 chromosomes believed to be carrying a β-hexosaminidase A α-subunit gene mutation. Ten had abnormalities which have been described previously. In the remaining 24 Tay-Sachs disease alleles, six novel mutations predicted to be deleterious were discovered. These include two small deletions (a single-base frameshift and a three-base deletion removing an amino acid), two different nonsense mutations, an initiation codon mutation (ATG→GTG), and a missense mutation (Arg499Cys) in a highly conserved residue. In addition, three presumed nondeleterious mutations were found.

Original languageEnglish (US)
Pages (from-to)834-841
Number of pages8
JournalAmerican Journal of Human Genetics
Volume50
Issue number4
StatePublished - Apr 1992
Externally publishedYes

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Hexosaminidase A
Mutation
Genes
beta-Hexosaminidase alpha Chain
GM2 Gangliosidosis
Tay-Sachs Disease
Chromosomes, Human, Pair 22
Chromosomes, Human, Pair 17
Initiator Codon
Nonsense Codon
Missense Mutation
Population
Alleles
Amino Acids
Polymerase Chain Reaction
DNA
Incidence

ASJC Scopus subject areas

  • Genetics

Cite this

Six novel deleterious and three neutral mutations in the gene encoding the α-subunit of hexosaminidase A in non-Jewish individuals. / Mules, Emilie H.; Hayflick, Susan; Miller, Carol S.; Reynolds, Linda W.; Thomas, George H.

In: American Journal of Human Genetics, Vol. 50, No. 4, 04.1992, p. 834-841.

Research output: Contribution to journalArticle

Mules, Emilie H. ; Hayflick, Susan ; Miller, Carol S. ; Reynolds, Linda W. ; Thomas, George H. / Six novel deleterious and three neutral mutations in the gene encoding the α-subunit of hexosaminidase A in non-Jewish individuals. In: American Journal of Human Genetics. 1992 ; Vol. 50, No. 4. pp. 834-841.
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