Abstract:
:GM(2) gangliosidoses are a group of panethnic lysosomal storage diseases in which GM(2) ganglioside accumulates in the lysosome due to a defect in one of three genes, two of which encode the alpha- or beta-subunits of beta- N -acetylhexosaminidase (Hex) A. A small inframe deletion mutation in the catalytic domain of the alpha-subunit of Hex has been found in five Turkish patients with infantile Tay-Sachs disease. To date it has not been detected in other populations and is the only mutation to be found in exon 10. It results in detectable levels of inactive alpha-protein in its precursor form. Because the alpha- and beta-subunits share 60% sequence identity, the Hex A and Hex B genes are believed to have arisen from a common ancestral gene. Thus the subunits must share very similar three-dimensional structures with conserved functional domains. Hex B, the beta-subunit homodimer is more stable than the heterodimeric Hex A, and much more stable than Hex S, the alpha homodimer. Thus, mutations that completely destabilize the alpha-subunit can often be partially rescued if expressed in the aligned positions in the beta-subunit. To better understand the severity of the Turkish HEXA mutation, we reproduced the 12 bp deletion mutation (1267-1278) in the beta-subunit cDNA. Western blot analysis of permanently transfected CHO cells expressing the mutant detected only the pro-form of the beta-subunit coupled with a total lack of detectable Hex B activity. These data indicate that the deletion of the four amino acids severely affects the folding of even the more stable beta-subunit, causing its retention in the endoplasmic reticulum and ultimate degradation.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Sinici I,Tropak MB,Mahuran DJ,Ozkara HAdoi
10.1023/B:BOLI.0000045759.12935.76keywords:
subject
Has Abstractpub_date
2004-01-01 00:00:00pages
747-56issue
6eissn
0141-8955issn
1573-2665pii
5383681journal_volume
27pub_type
杂志文章abstract::Mutations in genes encoding metabolic enzymes are often the cause of inherited diseases. Mutations usually affect the ability of proteins to fold properly, thus leading to enzyme loss of function. In this work, we explored the relationships between protein stability, aggregation, and degradation in vitro and inside ce...
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更新日期:1988-01-01 00:00:00
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更新日期:2009-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:1984-01-01 00:00:00
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journal_title:Journal of inherited metabolic disease
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更新日期:2014-09-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01799945
更新日期:1991-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s10545-011-9340-6
更新日期:2011-12-01 00:00:00
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doi:10.1002/jimd.12223
更新日期:2020-07-01 00:00:00
abstract::Neuropsychological assessment is essential in providing documentation of the untreated natural history of storage diseases associated with dementia and quantifying the effectiveness of treatment on central nervous system function. Baseline characterization and outcome of bone marrow transplantation (BMT) for three leu...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF00710053
更新日期:1995-01-01 00:00:00
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更新日期:2014-01-01 00:00:00
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更新日期:1997-09-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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更新日期:1980-01-01 00:00:00
abstract::Aspartylglycosaminuria (AGU, McKusick 20840) is a metabolic disorder affecting the catabolism of glycoproteins. It was first described in 1967, by Jenner and Pollitt, in two mentally retarded English siblings. Subsequently several cases were reported from Finland (Palo and Mattsson, 1970; Autio, 1972; Autio et al., 19...
journal_title:Journal of inherited metabolic disease
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更新日期:1982-01-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
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更新日期:2004-01-01 00:00:00
abstract::We report studies on two patients (1 and 2) with Hurler disease. They both had all of the non-neurological features of Hurler disease to a similar and extreme degree and similar signs of brain damage on computed tomography. However, intellectual function was unusually well-preserved in patient 1, but seriously and typ...
journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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更新日期:1986-01-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/BF01797915
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVES:To study the incidence of galactosaemia in the state of São Paulo and the benefit/cost (B/C) ratio of the introduction of neonatal screening for galactosaemia, comparing it with a selective approach. METHODS:An enzymatic-colorimetric assay was used for the screening of total galactose (TG) in a sample of 10...
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pub_type: 杂志文章
doi:10.1007/s10545-009-1112-1
更新日期:2009-12-01 00:00:00
abstract::Transaldolase (TAL) is an enzyme in the pentose phosphate pathway (PPP) that generates NADPH for protection against oxidative stress. While deficiency of other PPP enzymes, such as transketolase (TKT), are incompatible with mammalian cell survival, mice lacking TAL are viable and develop progressive liver disease attr...
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pub_type: 杂志文章
doi:10.1002/jimd.12197
更新日期:2020-05-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2013-05-01 00:00:00