A pseudodeficiency allele common in non-Jewish Tay-Sachs carriers: Implications for carrier screening

Journal Article · Thu Oct 01 00:00:00 EDT 1992 · American Journal of Human Genetics; (United States)

OSTI ID:5052185

Triggs-Raine, B L; Akerman, B R; Gravel, R A ^[1]; Mules, E H; Thomas, G H; Dowling, C E ^[2]; Kaback, M M; Lim-Steele, J S.T. ^[3]; Natowicz, M R ^[4]; Grebner, E E ^[5]; Navon, R R ^[6]; Welch, J P ^[7]; Greenberg, C R ^[8]

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1. McGill Univ.-Montreal Children's Hospital Research Institute, Montreal, Quebec (Canada)
2. Johns Hopkins School of Medicine, Baltimore, MD (United States)
3. Univ. of California, San Diego, CA (United States)
4. Eunice Kennedy Shriver Center for Mental Retardation, Waltham, MA (United States)
5. Thomas Jefferson Univ., Philadelphia, PA (United States)
6. Tel-Aviv Univ., Kfar-Sava (Israel)
7. Dalhousie Univ., Halifax, Nova, Scotia (Canada)
8. Univ. of Manitoba, Winnipeg (Canada)

Deficiency of [beta]-hexosaminidase A (Hex A) activity typically results in Tay-Sachs disease. However, healthy subjects found to be deficient in Hex A activity (i.e., pseudodeficient) by means of in vitro biochemical tests have been described. The authors analyzed the HEXA gene of one pseudodeficient subject and identified both a C[sub 739]-to-T substitution that changes Arg[sub 247][yields]Trp on one allele and a previously identified Tay-Sachs disease mutation of the second allele. Six additional pseudodeficient subjects were found to have the C[sub 739]-to-T but for none of 36 Jewish enzyme-defined carries who did not have one of three known mutations common to this group. The C[sub 739]-to-T allele, together with a [open quotes]true[close quotes] Tay-Sachs disease allele, causes Hex A pseudodeficiency. Given both the large proportion of non-Jewish carriers with this allele and that standard biochemical screening cannot differentiate between heterozygotes for the C[sub 739]-to-T mutations and Tay-Sachs disease carriers, DNA testing for this mutation in at-risk couples is essential. This could prevent unnecessary or incorrect prenatal diagnoses. 40 refs., 3 figs., 4 tabs.

• OSTI ID: 5052185
• Journal Information: American Journal of Human Genetics; (United States), Vol. 51:4; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GANGLIOSIDES
METABOLIC DISEASES
HUMAN POPULATIONS
SCREENING
HYDROLASES
GENE MUTATIONS
AMINO ACID SEQUENCE
DNA SEQUENCING
HEXOSAMINES
PHOSPHOLIPIDS
SPHINGOMYELINS
AMINES
CARBOHYDRATES
DISEASES
ENZYMES
ESTERS
GLYCOLIPIDS
HEXOSES
LIPIDS
MOLECULAR STRUCTURE
MONOSACCHARIDES
MUTATIONS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
POPULATIONS
PROTEINS
SACCHARIDES
STRUCTURAL CHEMICAL ANALYSIS
550400* - Genetics
550900 - Pathology
550200 - Biochemistry