Molecular basis of adult-onset and chronic G sub M2 gangliosidoses in patients of Ashkenazi Jewish origin: Substitution of serine for glycine at position 269 of the. alpha. -subunit of. beta. -hexosaminidase
- Univ. of California, Los Angeles (USA)
Chronic and adult-onset G{sub M2} gangliosidoses are neurological disorders caused by marked deficiency of the A isoenzyme of {beta}-hexosaminidase; they occur in the Ashkenazi Jewish population, though less frequently than classic (infantile) Tay-Sachs disease. Earlier biosynthetic studies had identified a defective {alpha}-subunit that failed to associate with the {beta}-subunit. The authors have now found a guanosine to adenosine transition at the 3{prime} end of exon 7, which causes substitution of serine for glycine at position 269 of the {alpha}-subunit. An RNase protection assay was used to localize the mutation to a segment of mRNA from fibroblasts of a patient with the adult-onset disorder. That segment of mRNA (after reverse transcription) and a corresponding segment of genomic DNA were amplified by the polymerase chain reaction and sequenced by the dideoxy method. The sequence analysis, together with an assay based on the loss of a ScrFI restriction site, showed that the patient was a compound heterozygote who had inherited the 269 (Gly {yields} Ser) mutation from his father and an allelic null mutation from his mother. The 269 (Gly {yields} Ser) mutation, in compound heterozygosity with a presumed null allele, was also found in fetal fibroblasts with an association-defective phenotype and in cells from five patients with chronic G{sub M2} gangliosidosis.
- OSTI ID:
- 5263216
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:7; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HEREDITARY DISEASES
ETIOLOGY
HEXOSYL TRANSFERASES
DNA BASE TRANSITIONS
MESSENGER-RNA
AUTORADIOGRAPHY
FIBROBLASTS
GANGLIOSIDES
GENE MUTATIONS
GLYCINE
NERVOUS SYSTEM DISEASES
PATIENTS
SERINE
AMINO ACIDS
ANIMAL CELLS
CARBOHYDRATES
CARBOXYLIC ACIDS
CONNECTIVE TISSUE CELLS
DISEASES
ENZYMES
GLYCOLIPIDS
GLYCOSYL TRANSFERASES
HYDROXY ACIDS
LIPIDS
MUTATIONS
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
RNA
SACCHARIDES
SOMATIC CELLS
TRANSFERASES
550401* - Genetics- Tracer Techniques