A double mutation in exon 6 of the [beta]-hexosaminidase [alpha] subunit in a patient with the B1 variant of Tay-Sachs disease

Journal Article · Thu Oct 01 04:00:00 EDT 1992 · American Journal of Human Genetics; (United States)

OSTI ID:5052235

Ainsworth, P J ^[1]; Coulter-Mackie, M B ^[2]

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1. Univ. of Western Ontario, Ontario (Canada) Child Health Research Institute, London, Ontario (Canada)
2. Univ. of Western Ontario, Ontario (Canada) Child Health Research Institute, London, Ontario (Canada) Children's Psychiatric Research Institute, London, Ontario (Canada)

The B1 variant form of Tay-Sachs disease is enzymologically unique in that the causative mutation(s) appear to affect the active site in the [alpha] subunit of [beta]-hexosaminidase A without altering its ability to associate with the [beta] subunit. Most previously reported B1 variant mutations were found in exon 5 within codon 178. The coding sequence of the [alpha] subunit gene of a patient with the B1 variant form was examined with a combination of reverse transcription of mRNA to cDNA, PCR, and dideoxy sequencing. A double mutation in exon 6 has been identified: a G[sub 574][yields]C transversion causing a val[sub 192][yields]leu change and a G[sub 598][yields] A transition resulting in a val[sub 200][yields]met alteration. The amplified cDNAs were otherwise normal throughout their sequence. The 574 and 598 alterations have been confirmed by amplification directly from genomic DNA from the patient and her mother. Transient-expression studies of the two exon 6 mutations (singly or together) in COS-1 cells show that the G[sub 574][yields]C change is sufficient to cause the loss of enzyme activity. The biochemical phenotype of the 574 alteration in transfection studies is consistent with that expected for a B1 variant mutation. As such, this mutation differs from previously reported B1 variant mutations, all of which occur in exon 5. 31 refs., 2 figs., 2 tabs.

• OSTI ID: 5052235
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 51:4; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

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