Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations
Metachromatic leukodystrophy (MLD) disorder is a rare lysosomal storage disorder that leads to severe neurological symptoms and an early death. MLD occurs due to the deficiency of enzyme arylsulfatase A (ARSA) in leukocytes, and patients with MLD excrete sulfatide in their urine. In this study, the...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2017
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| Online Access: | http://psasir.upm.edu.my/id/eprint/61916/1/Four%20novel%20ARSA%20gene%20mutations%20with%20pathogenic.pdf |
| _version_ | 1825932410147045376 |
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| author | Manshadi, Masoumeh Dehghan Kamalidehghan, Behnam Aryani, Omid Khalili, Elham Dadgar, Sepideh Tondar, Mahdi Ahmadipour, Fatemeh Goh, Yong Meng Houshmand, Massoud |
| author_facet | Manshadi, Masoumeh Dehghan Kamalidehghan, Behnam Aryani, Omid Khalili, Elham Dadgar, Sepideh Tondar, Mahdi Ahmadipour, Fatemeh Goh, Yong Meng Houshmand, Massoud |
| author_sort | Manshadi, Masoumeh Dehghan |
| collection | UPM |
| description | Metachromatic leukodystrophy (MLD) disorder is a rare lysosomal storage disorder that leads to severe neurological symptoms and an early death. MLD occurs due to the deficiency of enzyme arylsulfatase A (ARSA) in leukocytes, and patients with MLD excrete sulfatide in their urine. In this study, the ARSA gene in 12 non-consanguineous MLD patients and 40 healthy individuals was examined using polymerase chain reaction sequencing. Furthermore, the structural and functional effects of new mutations on ARSA were analyzed using SIFT (sorting intolerant from tolerant), I-Mutant 2, and PolyPhen bioinformatics software. Here, 4 new pathogenic homozygous mutations c.585G>T, c.661T>A, c.849C>G, and c.911A>G were detected. The consequence of this study has extended the genotypic spectrum of MLD patients, paving way to a more effective method for carrier detection and genetic counseling. |
| first_indexed | 2024-03-06T09:41:36Z |
| format | Article |
| id | upm.eprints-61916 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T09:41:36Z |
| publishDate | 2017 |
| publisher | Dove Medical Press |
| record_format | dspace |
| spelling | upm.eprints-619162019-02-27T06:45:47Z http://psasir.upm.edu.my/id/eprint/61916/ Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations Manshadi, Masoumeh Dehghan Kamalidehghan, Behnam Aryani, Omid Khalili, Elham Dadgar, Sepideh Tondar, Mahdi Ahmadipour, Fatemeh Goh, Yong Meng Houshmand, Massoud Metachromatic leukodystrophy (MLD) disorder is a rare lysosomal storage disorder that leads to severe neurological symptoms and an early death. MLD occurs due to the deficiency of enzyme arylsulfatase A (ARSA) in leukocytes, and patients with MLD excrete sulfatide in their urine. In this study, the ARSA gene in 12 non-consanguineous MLD patients and 40 healthy individuals was examined using polymerase chain reaction sequencing. Furthermore, the structural and functional effects of new mutations on ARSA were analyzed using SIFT (sorting intolerant from tolerant), I-Mutant 2, and PolyPhen bioinformatics software. Here, 4 new pathogenic homozygous mutations c.585G>T, c.661T>A, c.849C>G, and c.911A>G were detected. The consequence of this study has extended the genotypic spectrum of MLD patients, paving way to a more effective method for carrier detection and genetic counseling. Dove Medical Press 2017-06 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/61916/1/Four%20novel%20ARSA%20gene%20mutations%20with%20pathogenic.pdf Manshadi, Masoumeh Dehghan and Kamalidehghan, Behnam and Aryani, Omid and Khalili, Elham and Dadgar, Sepideh and Tondar, Mahdi and Ahmadipour, Fatemeh and Goh, Yong Meng and Houshmand, Massoud (2017) Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations. Therapeutics and Clinical Risk Management, 13. 725 - 731. ISSN 1176-6336; ESSN: 1178-203X https://www.dovepress.com/four-novel-arsa-gene-mutations-with-pathogenic-impacts-on-metachromati-peer-reviewed-article-TCRM 10.2147/TCRM.S119967 |
| spellingShingle | Manshadi, Masoumeh Dehghan Kamalidehghan, Behnam Aryani, Omid Khalili, Elham Dadgar, Sepideh Tondar, Mahdi Ahmadipour, Fatemeh Goh, Yong Meng Houshmand, Massoud Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations |
| title | Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations |
| title_full | Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations |
| title_fullStr | Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations |
| title_full_unstemmed | Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations |
| title_short | Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations |
| title_sort | four novel arsa gene mutations with pathogenic impacts on metachromatic leukodystrophy a bioinformatics approach to predict pathogenic mutations |
| url | http://psasir.upm.edu.my/id/eprint/61916/1/Four%20novel%20ARSA%20gene%20mutations%20with%20pathogenic.pdf |
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