Identification of GM2‐gangliosidosis B1 variant carriers

Ribeiro, Maria Gil; Pinto, Rui; Oliveira, Pedro; Sá-Miranda, Clara

doi:10.1007/bf00711518

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…Previous studies suggested that variant B1 is more common than expected in Portugal (Ribeiro et al, 1993;Pinto et al, 2004). Therefore, we decided to set up a method that would be suitable for population screening of HEXA gene mutation c.533G > A.…”

Section: Introductionmentioning

confidence: 99%

Rapid and Cost-Effective Method for the Detection of the c.533G>A Mutation in theHEXAGene

Ribeiro

Duarte²,

Amaral³

2011

Genetic Testing and Molecular Biomarkers

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Tay-Sachs disease is a rare autosomal recessive neurodegenerative disorder that results from mutations in the HEXA gene, leading to β-hexosaminidase A (HexA) α subunit deficiency. An unusual variant of Tay-Sachs disease is known as the B1 variant. Previous studies indicated that, in northern Portugal, this is not only the most common variant but also one of the most prevalent lysosomal storage diseases. Additionally, this variant might also show a higher prevalence in populations of Portuguese and Spanish ancestry. A single mutation is invariably present in at least one of the alleles of B1 variant patients, HEXA mutation c.533G >A. To implement a method for c.533G >A testing in individuals and populations, we have optimized two distinct mutation analysis techniques, one based on restriction fragment length polymorphism analysis and the other based on allelic discrimination. We present the comparison of both methods and their advantages. Mutation screening by allelic discrimination proved to be particularly useful for the studying of large samples of individuals. It is time saving and highly reproducible, and under the conditions used, its cost is lower than the cost of polymerase chain reaction-based restriction fragment length polymorphism analysis.

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Section: Introductionmentioning

confidence: 99%

Rapid and Cost-Effective Method for the Detection of the c.533G>A Mutation in theHEXAGene

Ribeiro

Duarte²,

Amaral³

2011

Genetic Testing and Molecular Biomarkers

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Biochemical characterization of the GM2 gangliosidosis B1 variant

Tutor

2004

Braz J Med Biol Res

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The deficiency of the A isoenzyme of ß-hexosaminidase (Hex) produced by different mutations of the gene that codes for the α subunit (Tay-Sachs disease) has two variants with enzymological differences: the B variant consists of the absence of Hex A isoenzyme and the B1 variant produces an inactive Hex A isoenzyme for the hydrolysis of the GM2 ganglioside and synthetic substrates with negative charge. In contrast to the early childhood form of the B variant, the B1 variant appears at a later clinical stage (3 to 7 years of age) with neurodegenerative symptoms leading to the death of the patient in the second decade of life. The most frequent mutation responsible for the GM2 gangliosidosis B1 variant is R178H, which has a widespread geographic and ethnic distribution. The highest incidence has been described in Portugal, which has been suggested as the point of origin of this mutation. Biochemical characterization of this lysosomal disease is carried out using negatively charged synthetic α subunit-specific sulfated substrates, since Hex A isoenzyme heat-inactivation assays are not applicable. However, the determination of the apparent activation energy of Hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-ß-D-glucosaminide, may offer a valid alternative. The presence of an α subunit in the αß heterodimer Hex A means that its activation energy (41.8 kJ/mol) is significantly lower than that of the ßß homodimer Hex B (75.1 kJ/mol); however, as mutation inactivates the α subunit, the Hex A of the B1 variant presents an activation energy that is similar to that of the Hex B isoenzyme. Correspondence

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Identification of GM2‐gangliosidosis B1 variant carriers

Cited by 2 publications

References 10 publications

Rapid and Cost-Effective Method for the Detection of the c.533G>A Mutation in theHEXAGene

Rapid and Cost-Effective Method for the Detection of the c.533G>A Mutation in theHEXAGene

Biochemical characterization of the GM2 gangliosidosis B1 variant

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