A Novel Functional Missense Mutation p.T219A in Type 1 Gaucher′s Disease
Background: Gaucher's disease (GD) is an autosomal recessive disorder caused by a deficiency of acid β-glucosidase (glucocerebrosidase [GBA]) that results in the accumulation of glucocerebroside within macrophages. Many mutations have been reported to be associated with this disorder. This stud...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2016-01-01
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| Series: | Chinese Medical Journal |
| Subjects: | |
| Online Access: | http://www.cmj.org/article.asp?issn=0366-6999;year=2016;volume=129;issue=9;spage=1072;epage=1077;aulast=Liu |
| _version_ | 1818130039747641344 |
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| author | Lin-Yu Liu Fei Liu Si-Chen Du Sha-Yi Jiang Hui-Jun Wang Jin Zhang Wei Wang Duan Ma |
| author_facet | Lin-Yu Liu Fei Liu Si-Chen Du Sha-Yi Jiang Hui-Jun Wang Jin Zhang Wei Wang Duan Ma |
| author_sort | Lin-Yu Liu |
| collection | DOAJ |
| description | Background: Gaucher's disease (GD) is an autosomal recessive disorder caused by a deficiency of acid β-glucosidase (glucocerebrosidase [GBA]) that results in the accumulation of glucocerebroside within macrophages. Many mutations have been reported to be associated with this disorder. This study aimed to discover more mutations and provide data for the genetic pattern of the gene, which will help the development of quick and accurate genetic diagnostic tools for this disease.
Methods: Genomic DNA was obtained from peripheral blood leukocytes of the patient and Sanger sequencing is used to sequence GBA gene. Sequence alignments of mammalian β-GBA (GCase) and three-dimensional protein structure prediction of the mutation were made. A construct of this mutant and its compound heterozygous counterpart were used to measure GCase in vitro.
Results: GCase is relatively conserved at p.T219A. This novel mutation differs from its wild-type in structure. Moreover, it also causes a reduction in GCase enzyme activity.
Conclusion: This novel mutation (c.655A>G, p.T219A) is a pathogenic missense mutation, which contributes to GD. |
| first_indexed | 2024-12-11T07:58:42Z |
| format | Article |
| id | doaj.art-d2d3487ded61493b9ca4723256926b81 |
| institution | Directory Open Access Journal |
| issn | 0366-6999 |
| language | English |
| last_indexed | 2024-12-11T07:58:42Z |
| publishDate | 2016-01-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Chinese Medical Journal |
| spelling | doaj.art-d2d3487ded61493b9ca4723256926b812022-12-22T01:15:11ZengWolters KluwerChinese Medical Journal0366-69992016-01-0112991072107710.4103/0366-6999.180523A Novel Functional Missense Mutation p.T219A in Type 1 Gaucher′s DiseaseLin-Yu LiuFei LiuSi-Chen DuSha-Yi JiangHui-Jun WangJin ZhangWei WangDuan MaBackground: Gaucher's disease (GD) is an autosomal recessive disorder caused by a deficiency of acid β-glucosidase (glucocerebrosidase [GBA]) that results in the accumulation of glucocerebroside within macrophages. Many mutations have been reported to be associated with this disorder. This study aimed to discover more mutations and provide data for the genetic pattern of the gene, which will help the development of quick and accurate genetic diagnostic tools for this disease. Methods: Genomic DNA was obtained from peripheral blood leukocytes of the patient and Sanger sequencing is used to sequence GBA gene. Sequence alignments of mammalian β-GBA (GCase) and three-dimensional protein structure prediction of the mutation were made. A construct of this mutant and its compound heterozygous counterpart were used to measure GCase in vitro. Results: GCase is relatively conserved at p.T219A. This novel mutation differs from its wild-type in structure. Moreover, it also causes a reduction in GCase enzyme activity. Conclusion: This novel mutation (c.655A>G, p.T219A) is a pathogenic missense mutation, which contributes to GD.http://www.cmj.org/article.asp?issn=0366-6999;year=2016;volume=129;issue=9;spage=1072;epage=1077;aulast=LiuGaucher's Disease; GCase; Genetics; Novel Missense Mutation |
| spellingShingle | Lin-Yu Liu Fei Liu Si-Chen Du Sha-Yi Jiang Hui-Jun Wang Jin Zhang Wei Wang Duan Ma A Novel Functional Missense Mutation p.T219A in Type 1 Gaucher′s Disease Chinese Medical Journal Gaucher's Disease; GCase; Genetics; Novel Missense Mutation |
| title | A Novel Functional Missense Mutation p.T219A in Type 1 Gaucher′s Disease |
| title_full | A Novel Functional Missense Mutation p.T219A in Type 1 Gaucher′s Disease |
| title_fullStr | A Novel Functional Missense Mutation p.T219A in Type 1 Gaucher′s Disease |
| title_full_unstemmed | A Novel Functional Missense Mutation p.T219A in Type 1 Gaucher′s Disease |
| title_short | A Novel Functional Missense Mutation p.T219A in Type 1 Gaucher′s Disease |
| title_sort | novel functional missense mutation p t219a in type 1 gaucher s disease |
| topic | Gaucher's Disease; GCase; Genetics; Novel Missense Mutation |
| url | http://www.cmj.org/article.asp?issn=0366-6999;year=2016;volume=129;issue=9;spage=1072;epage=1077;aulast=Liu |
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