Molecular characterization of both alleles in an unusual Tay-Sachs disease BI variant

Journal Article · Wed Jun 01 04:00:00 EDT 1994 · American Journal of Human Genetics; (United States)

OSTI ID:7199761

Coulter-Mackie, M B ^[1]

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1. Univ. of Western Ontario, London (Canada) Child Health Research Institute, Children's Hospital of Western Ontario, London (Canada) Child Parent Resource Institute, London, Ontario (Canada)

In a recent report, the authors described an exon 6 mutation in a Tay-Sachs B1 variant patient, first reported by Gordon et al. (1988), who displayed a typical B1 variant biochemical phenotype - i.e., (a) significant levels of hexosaminidase A (Hex A) activity in an assay with a neutral synthetic substrate, 4-methylumbelliferyl-[beta]-N-acetylglucosamide, and (b) <2% of control Hex A in a test on the sulfated substrate, 4-methylumbelliferyl-[beta]-N-acetylglucosamide-6-sulfate. The patient was found to carry a double mutation (G[sub 574][yields]C [val[sub 192][yields]leu] and G[sub 598][yields]A [val[sub 200][yields]met]) inherited from her mother. Only the 574 mutation produced a deleterious effect on Hex A activity in transfected COS0-1 cells, producing a B1 variant biochemical phenotype. The paternal allele apparently caused decreased abundance of mRNA, since no candidate paternal mutations were found in cloned reverse transcription-PCR (RT-PCR) products in the reported study. The biochemical phenotype of the original patient and the properties of the cDNA carrying the G[sub 574] [yields] C mutation in transient expression studies were compatible with a B1 variant mutation. The possibility remained that there might be some contribution from the paternal allele to the patient's phenotype. However, the paternal allele produces relatively low yields of a largely mis-spliced mRNA whose product would not be functional. Therefore, the G[sub 574] [yields] C (val[yields]leu) mutation in the maternal allele is clearly confirmed as a B1 variant mutation with all the ramifications for the substrate binding site and/or catalytic center that this implies.

• OSTI ID: 7199761
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 54:6; 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
CARBOHYDRATES
CHEMICAL REACTIONS
DECOMPOSITION
DISEASES
ENZYMATIC HYDROLYSIS
ENZYMES
ESTERS
GENE MUTATIONS
HEXOSAMINES
HEXOSES
HYDROLYSIS
LIPIDS
LYSIS
METABOLIC DISEASES
MONOSACCHARIDES
MUTATIONS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHOSPHOLIPIDS
PROTEINS
SACCHARIDES
SOLVOLYSIS
SPHINGOMYELINS