Fabry disease: Biochemical, pathological and structural studies of the α-galactosidase A with E66Q amino acid substitution
書誌事項
- 公開日
- 2012-04
- 資源種別
- journal article
- 権利情報
-
- https://www.elsevier.com/tdm/userlicense/1.0/
- https://www.elsevier.com/legal/tdmrep-license
- https://doi.org/10.15223/policy-017
- https://doi.org/10.15223/policy-037
- https://doi.org/10.15223/policy-012
- https://doi.org/10.15223/policy-029
- https://doi.org/10.15223/policy-004
- DOI
-
- 10.1016/j.ymgme.2012.01.010
- 公開者
- Elsevier BV
この論文をさがす
説明
Recently, male subjects harboring the c.196GC nucleotide change which leads to the E66Q enzyme having low α-galactosidase A (GLA) activity have been identified at an unexpectedly high frequency on Japanese and Korean screening for Fabry disease involving dry blood spots and plasma/serum samples. Individuals with the E66Q enzyme have been suspected to have the later-onset Fabry disease phenotype leading to renal and cardiac disease. However, there has been no convincing evidence for this. To determine whether c.196GC (E66Q) is disease-causing or not, we performed biochemical, pathological and structural studies. It was predicted that the E66Q amino acid substitution causes a small conformational change on the molecular surface of GLA, which leads to instability of the enzyme protein. However, biochemical studies revealed that subjects harboring the E66Q enzyme exhibited relatively high residual enzyme activity in white blood cells, and that there was no accumulation of globotriaosylceramide in cultured fibroblasts or an increased level of plasma globotriaosylsphingosine in these subjects. An electron microscopic examination did not reveal any pathological changes specific to Fabry disease in biopsied skin tissues from a male subject with the E66Q enzyme. These results strongly suggest that the c.196GC is not a pathogenic mutation but is a functional polymorphism.
収録刊行物
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- Molecular Genetics and Metabolism
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Molecular Genetics and Metabolism 105 (4), 615-620, 2012-04
Elsevier BV
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キーワード
- Male
- Models, Molecular
- Heterozygote
- DNA Mutational Analysis
- Immunoblotting
- Real-Time Polymerase Chain Reaction
- Asian People
- Humans
- Cells, Cultured
- Aged
- Skin
- Aged, 80 and over
- Trihexosylceramides
- Fibroblasts
- Middle Aged
- Microscopy, Electron
- Phenotype
- Amino Acid Substitution
- Child, Preschool
- alpha-Galactosidase
- Mutation
- Fabry Disease
詳細情報 詳細情報について
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- CRID
- 1360004232561707776
-
- NII論文ID
- 20001581219
-
- ISSN
- 10967192
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- PubMed
- 22305854
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- 資料種別
- journal article
-
- データソース種別
-
- Crossref
- CiNii Articles
- KAKEN
- OpenAIRE
