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First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan

Leukodystrophies (LDs) are heterogeneous genetic disorders characterized by abnormal white matter in the central nervous system. Some of the LDs are progressive and often fatal. In general, LD is primarily diagnosed based on the neuroimaging; however, definitive diagnosis of the LD type is done usin...

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Autor principal: Froukh, Tawfiq
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374869/
https://www.ncbi.nlm.nih.gov/pubmed/30834272
http://dx.doi.org/10.1155/2019/7235914
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author Froukh, Tawfiq
author_facet Froukh, Tawfiq
author_sort Froukh, Tawfiq
collection PubMed
description Leukodystrophies (LDs) are heterogeneous genetic disorders characterized by abnormal white matter in the central nervous system. Some of the LDs are progressive and often fatal. In general, LD is primarily diagnosed based on the neuroimaging; however, definitive diagnosis of the LD type is done using genetic testing such as next-generation sequencing. The aim of this study is to identify the genetic causes of LD in two independent Jordanian cases that exhibit MRI findings confirming LD with no definitive diagnosis using whole exome sequencing (WES). The most likely causative variants were identified. In one case, the homozygous pathogenic variant NM_000049.2:c.914C>A;p.Ala305Glu, which is previously reported in ClinVar, in the gene ASPA was identified causing Canavan disease. In the second case, the homozygous novel variant NM_000487.5:c.256C>G;p.Arg86Gly in the gene ARSA was identified causing metachromatic leukodystrophy. The two variants segregate in their families. The phenotypes of the two studied cases overlap with assigned diseases. The present study raises the importance of using WES to identify the precise neurodevelopmental diseases in Jordan.
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spelling pubmed-63748692019-03-04 First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan Froukh, Tawfiq Biomed Res Int Research Article Leukodystrophies (LDs) are heterogeneous genetic disorders characterized by abnormal white matter in the central nervous system. Some of the LDs are progressive and often fatal. In general, LD is primarily diagnosed based on the neuroimaging; however, definitive diagnosis of the LD type is done using genetic testing such as next-generation sequencing. The aim of this study is to identify the genetic causes of LD in two independent Jordanian cases that exhibit MRI findings confirming LD with no definitive diagnosis using whole exome sequencing (WES). The most likely causative variants were identified. In one case, the homozygous pathogenic variant NM_000049.2:c.914C>A;p.Ala305Glu, which is previously reported in ClinVar, in the gene ASPA was identified causing Canavan disease. In the second case, the homozygous novel variant NM_000487.5:c.256C>G;p.Arg86Gly in the gene ARSA was identified causing metachromatic leukodystrophy. The two variants segregate in their families. The phenotypes of the two studied cases overlap with assigned diseases. The present study raises the importance of using WES to identify the precise neurodevelopmental diseases in Jordan. Hindawi 2019-01-30 /pmc/articles/PMC6374869/ /pubmed/30834272 http://dx.doi.org/10.1155/2019/7235914 Text en Copyright © 2019 Tawfiq Froukh. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Froukh, Tawfiq
First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan
title First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan
title_full First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan
title_fullStr First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan
title_full_unstemmed First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan
title_short First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan
title_sort first record mutations in the genes aspa and arsa causing leukodystrophy in jordan
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374869/
https://www.ncbi.nlm.nih.gov/pubmed/30834272
http://dx.doi.org/10.1155/2019/7235914
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