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

E. H. Mules, S. Hayflick, C. S. Miller, L. W. Reynolds, G. H. Thomas

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Initial investigations demonstrated that only 3/34 'Tay-Sachs chromosomes' in 22 unrelated, non-Jewish patients or carriers of some form of G(M2)- 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 - Jan 1 1992

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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