Distribution of a pseudodeficiency allele among Tay-Sachs carriers

Journal Article · Sun Aug 01 04:00:00 EDT 1993 · American Journal of Human Genetics; (United States)

OSTI ID:5914424

Tomczak, J; Grebner, E E ^[1]; Boogen, C ^[2]

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1. Thomas Jefferson Univ., Philadelphia, PA (United States)
2. Univ. of Essen Medical School (Germany)

Recently Triggs-Raine et al. (1992) identified a new mutation in the gene coding for the [alpha]-subunit of [beta]-hexosaminidase A (hex A), the enzyme whose deficiency causes Tay-Sachs disease. This mutation, a C[sub 739]-to-T transition in exon 7, results in an altered enzyme that is active (albeit at reduced levels) in cells but that has essentially no activity in serum. This so-called pseudodeficient allele was first detected in compound heterozygotes who also carried a Tay-Sachs disease allele and therefore had no detectable hex A in their serum but who were in good health. Carriers of this apparently benign mutation are generally indistinguishable from carriers of a lethal mutation by means of routine enzyme-based screening tests, because the product of the pseudodeficient allele is not detectable in serum and has decreased activity in cells. This suggests that some individuals who have been classified as Tay-Sachs carriers are actually carriers of the pseudodeficient allele and are not at risk to have a child affected with Tay-Sachs disease. The pseudodeficient allele may also be responsible for some inconclusive diagnoses, where leukocyte values fall below the normal range but are still above the carrier range. The fact that there are now two mutant alleles (the psuedodeficient and the adult) that are indistinguishable from the lethal infantile mutations by means of enzyme assay yet that are phenotypically very different and that together may account for as much as 12% of enzyme-defined carriers on the basis of the data here suggests that DNA analysis should be part of a comprehensive screening program. It will be particularly useful to identify the mutations in couples at risk, before they undergo prenatal diagnosis. DNA analysis will also resolve some inconclusive diagnoses.

• OSTI ID: 5914424
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 53:2; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
AMINES
BIOLOGICAL VARIABILITY
CARBOHYDRATES
CEREBROSIDES
CHEMICAL REACTIONS
DECOMPOSITION
DISEASES
ENZYMATIC HYDROLYSIS
ENZYMES
ESTERS
GANGLIOSIDES
GENE MUTATIONS
GENETIC VARIABILITY
GLYCOLIPIDS
HEREDITARY DISEASES
HEXOSAMINES
HEXOSES
HUMAN POPULATIONS
HYDROLYSIS
LIPIDS
LYSIS
METABOLIC DISEASES
MONOSACCHARIDES
MUTATIONS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHOSPHOLIPIDS
POPULATIONS
PROTEINS
SACCHARIDES
SCREENING
SOLVOLYSIS
SPHINGOMYELINS