Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations

Masoumeh Dehghan Manshadi,1 Behnam Kamalidehghan,2,3 Omid Aryani,1 Elham Khalili,1 Sepideh Dadgar,1 Mahdi Tondar,4 Fatemeh Ahmadipour,5 Goh Yong Meng,6 Massoud Houshmand1,31Department of Medical Genetics, Special Medical Center, Tehran, Iran; 2Medical Genetics Department, School of Medicine, Shahid...

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Autores principales:	Dehghan Manshadi M, Kamalidehghan B, Aryani O, Khalili E, Dadgar S, Tondar M, Ahmadipour F, Yong Meng G, Houshmand M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Metachromatic leukodystrophy (MLD) ASA gene new pathogenic mutations Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d2b84d2229f94566b80dd08662d108f9
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spelling	oai:doaj.org-article:d2b84d2229f94566b80dd08662d108f92021-12-02T11:28:24ZFour novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations1178-203Xhttps://doaj.org/article/d2b84d2229f94566b80dd08662d108f92017-06-01T00:00:00Zhttps://www.dovepress.com/four-novel-arsa-gene-mutations-with-pathogenic-impacts-on-metachromati-peer-reviewed-article-TCRMhttps://doaj.org/toc/1178-203XMasoumeh Dehghan Manshadi,1 Behnam Kamalidehghan,2,3 Omid Aryani,1 Elham Khalili,1 Sepideh Dadgar,1 Mahdi Tondar,4 Fatemeh Ahmadipour,5 Goh Yong Meng,6 Massoud Houshmand1,31Department of Medical Genetics, Special Medical Center, Tehran, Iran; 2Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; 4Department of Biochemistry and Molecular & Cellular Biology, School of Medicine, Georgetown University, Washington, DC, USA; 5Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 6Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia Abstract: 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. Keywords: psychomotor regression, demyelinating, gait abnormality and impairment, metachromatic leukodystrophy (MLD), behavioral disturbancesDehghan Manshadi MKamalidehghan BAryani OKhalili EDadgar STondar MAhmadipour FYong Meng GHoushmand MDove Medical PressarticleMetachromatic leukodystrophy (MLD)ASA genenew pathogenic mutationsTherapeutics. PharmacologyRM1-950ENTherapeutics and Clinical Risk Management, Vol Volume 13, Pp 725-731 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Metachromatic leukodystrophy (MLD) ASA gene new pathogenic mutations Therapeutics. Pharmacology RM1-950
spellingShingle	Metachromatic leukodystrophy (MLD) ASA gene new pathogenic mutations Therapeutics. Pharmacology RM1-950 Dehghan Manshadi M Kamalidehghan B Aryani O Khalili E Dadgar S Tondar M Ahmadipour F Yong Meng G Houshmand M Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations
description	Masoumeh Dehghan Manshadi,1 Behnam Kamalidehghan,2,3 Omid Aryani,1 Elham Khalili,1 Sepideh Dadgar,1 Mahdi Tondar,4 Fatemeh Ahmadipour,5 Goh Yong Meng,6 Massoud Houshmand1,31Department of Medical Genetics, Special Medical Center, Tehran, Iran; 2Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; 4Department of Biochemistry and Molecular & Cellular Biology, School of Medicine, Georgetown University, Washington, DC, USA; 5Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 6Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Selangor, Malaysia Abstract: 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. Keywords: psychomotor regression, demyelinating, gait abnormality and impairment, metachromatic leukodystrophy (MLD), behavioral disturbances
format	article
author	Dehghan Manshadi M Kamalidehghan B Aryani O Khalili E Dadgar S Tondar M Ahmadipour F Yong Meng G Houshmand M
author_facet	Dehghan Manshadi M Kamalidehghan B Aryani O Khalili E Dadgar S Tondar M Ahmadipour F Yong Meng G Houshmand M
author_sort	Dehghan Manshadi M
title	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_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_sort	four novel arsa gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/d2b84d2229f94566b80dd08662d108f9
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Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: a bioinformatics approach to predict pathogenic mutations

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