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Primary Literature Review
Tay-Sachs Disease-Causing Mutations and Neutral Polymorphisms in the Hex A Gene
Myerowitz, R. [1]
Tay-Sachs disease (TSD) is a neurodegenerative disorder that can lead to death. This disease is caused by mutations in the HEXA gene that leave the body unable to produce an enzyme known as hexosaminidase-A. As a result of the enzyme deficiency, the accumulation of lipid called GM2 ganglioside in the central nervous system causes mental and motor deterioration. However, there is no curative treatment currently.
In this article, Rachel discussed 78 different mutations which have been found in the HEXA gene. The author categorized 67 out of these 78 different mutations as disease causing. Hence, the clinical heterogeneity manifestations of TSD are due to these mutations which affect the catalytic activity of β-hexosaminidase in variable degrees. The author also mentions that among those recognized mutations, the missense mutations (substitution of amino acids) are the most common mutation found in the HEXA gene. Most of these disease-causing mutations in the HEXA gene result in severe classic infantile TSD. The associated mutations with later onset TSD have been identified too.
Furthermore, the author highlighted that an enzymatic assay for HEXA is the preferred method used to screen for carriers of TSD. Identification of related mutations and the correlation between the mutations and the TSD phenotypes has provide more accurate carrier information and make prenatal diagnosis possible. Hence, in the future, it is important to get the precise picture of the amino acid residues involved in important biological functions of HEXA such as mechanism of catalysis.
Myerowitz, R. [1]
Tay-Sachs disease (TSD) is a neurodegenerative disorder that can lead to death. This disease is caused by mutations in the HEXA gene that leave the body unable to produce an enzyme known as hexosaminidase-A. As a result of the enzyme deficiency, the accumulation of lipid called GM2 ganglioside in the central nervous system causes mental and motor deterioration. However, there is no curative treatment currently.
In this article, Rachel discussed 78 different mutations which have been found in the HEXA gene. The author categorized 67 out of these 78 different mutations as disease causing. Hence, the clinical heterogeneity manifestations of TSD are due to these mutations which affect the catalytic activity of β-hexosaminidase in variable degrees. The author also mentions that among those recognized mutations, the missense mutations (substitution of amino acids) are the most common mutation found in the HEXA gene. Most of these disease-causing mutations in the HEXA gene result in severe classic infantile TSD. The associated mutations with later onset TSD have been identified too.
Furthermore, the author highlighted that an enzymatic assay for HEXA is the preferred method used to screen for carriers of TSD. Identification of related mutations and the correlation between the mutations and the TSD phenotypes has provide more accurate carrier information and make prenatal diagnosis possible. Hence, in the future, it is important to get the precise picture of the amino acid residues involved in important biological functions of HEXA such as mechanism of catalysis.
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tay-sachs_disease-causing_mutations_and_neutral-1997.pdf | |
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References
1. Myerowitz, R. (1997). Tay-sachs disease-causing mutations and neutral polymorphisms in the hex a gene. Human Mutation, 9(3), 195-208. Retreived March 1, 2012 from http://onlinelibrary.wiley.com.ezproxy.library.wisc.edu/doi/10.1002/(SICI)1098-1004(1997)9:3%3C195::AID-HUMU1%3E3.0.CO;2-7/pdf
2. Zeng, B. , Torres, P. , Viner, T. , Wang, Z. , Raghavan, S. , et al. (2008). Spontaneous appearance of tay-sachs disease in an animal model. Mol Genet Metab, 95(1-2), 59-52. doi: 10.1016/j.ymgme.2008.06.010
2. Zeng, B. , Torres, P. , Viner, T. , Wang, Z. , Raghavan, S. , et al. (2008). Spontaneous appearance of tay-sachs disease in an animal model. Mol Genet Metab, 95(1-2), 59-52. doi: 10.1016/j.ymgme.2008.06.010