Detection of Mosaic Variants in Mothers of MPS II Patients by Next Generation Sequencing

Mucopolysaccharidosis type II is an X-linked lysosomal storage disorder caused by mutations in the IDS gene that encodes the iduronate-2-sulfatase enzyme. The IDS gene is located on the long arm of the X-chromosome, comprising 9 exons, spanning approximately 24 kb. The analysis of carriers, in addit...

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Autores principales:	Alice Brinckmann Oliveira Netto, Ana Carolina Brusius-Facchin, Sandra Leistner-Segal, Francyne Kubaski, Juliana Josahkian, Roberto Giugliani
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	mosaicism mucopolysaccharidosis type II hunter syndrome next-generation sequencing IDS gene x-linked disease Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3b22f180790947778d87aeca9c971d99
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spelling	oai:doaj.org-article:3b22f180790947778d87aeca9c971d992021-11-05T05:27:52ZDetection of Mosaic Variants in Mothers of MPS II Patients by Next Generation Sequencing2296-889X10.3389/fmolb.2021.789350https://doaj.org/article/3b22f180790947778d87aeca9c971d992021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.789350/fullhttps://doaj.org/toc/2296-889XMucopolysaccharidosis type II is an X-linked lysosomal storage disorder caused by mutations in the IDS gene that encodes the iduronate-2-sulfatase enzyme. The IDS gene is located on the long arm of the X-chromosome, comprising 9 exons, spanning approximately 24 kb. The analysis of carriers, in addition to detecting mutations in patients, is essential for genetic counseling, since the risk of recurrence for male children is 50%. Mosaicism is a well-known phenomenon described in many genetic disorders caused by a variety of mechanisms that occur when a mutation arises in the early development of an embryo. Sanger sequencing is limited in detecting somatic mosaicism and sequence change levels of less than 20% may be missed. The Next Generation Sequencing (NGS) has been increasingly used in diagnosis. It is a sensitive and fast method for the detection of somatic mosaicism. Compared to Sanger sequencing, which represents a cumulative signal, NGS technology analyzes the sequence of each DNA read in a sample. NGS might therefore facilitate the detection of mosaicism in mothers of MPS II patients. The aim of this study was to reanalyze, by NGS, all MPS II mothers that showed to be non-carriers by Sanger analysis. Twelve non-carriers were selected for the reanalysis on the Ion PGM and Ion Torrent S5 platform, using a custom panel that includes the IDS gene. Results were visualized in the Integrative Genomics Viewer (IGV). We were able to detected the presence of the variant previously found in the index case in three of the mothers, with frequencies ranging between 13 and 49% of the reads. These results suggest the possibility of mosaicism in the mothers. The use of a more sensitive technology for detecting low-level mosaic mutations is essential for accurate recurrence-risk estimates. In our study, the NGS analysis showed to be an effective methodology to detect the mosaic event.Alice Brinckmann Oliveira NettoAlice Brinckmann Oliveira NettoAna Carolina Brusius-FacchinAna Carolina Brusius-FacchinAna Carolina Brusius-FacchinSandra Leistner-SegalFrancyne KubaskiFrancyne KubaskiFrancyne KubaskiFrancyne KubaskiJuliana JosahkianJuliana JosahkianRoberto GiuglianiRoberto GiuglianiRoberto GiuglianiRoberto GiuglianiFrontiers Media S.A.articlemosaicismmucopolysaccharidosis type IIhunter syndromenext-generation sequencingIDS genex-linked diseaseBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mosaicism mucopolysaccharidosis type II hunter syndrome next-generation sequencing IDS gene x-linked disease Biology (General) QH301-705.5
spellingShingle	mosaicism mucopolysaccharidosis type II hunter syndrome next-generation sequencing IDS gene x-linked disease Biology (General) QH301-705.5 Alice Brinckmann Oliveira Netto Alice Brinckmann Oliveira Netto Ana Carolina Brusius-Facchin Ana Carolina Brusius-Facchin Ana Carolina Brusius-Facchin Sandra Leistner-Segal Francyne Kubaski Francyne Kubaski Francyne Kubaski Francyne Kubaski Juliana Josahkian Juliana Josahkian Roberto Giugliani Roberto Giugliani Roberto Giugliani Roberto Giugliani Detection of Mosaic Variants in Mothers of MPS II Patients by Next Generation Sequencing
description	Mucopolysaccharidosis type II is an X-linked lysosomal storage disorder caused by mutations in the IDS gene that encodes the iduronate-2-sulfatase enzyme. The IDS gene is located on the long arm of the X-chromosome, comprising 9 exons, spanning approximately 24 kb. The analysis of carriers, in addition to detecting mutations in patients, is essential for genetic counseling, since the risk of recurrence for male children is 50%. Mosaicism is a well-known phenomenon described in many genetic disorders caused by a variety of mechanisms that occur when a mutation arises in the early development of an embryo. Sanger sequencing is limited in detecting somatic mosaicism and sequence change levels of less than 20% may be missed. The Next Generation Sequencing (NGS) has been increasingly used in diagnosis. It is a sensitive and fast method for the detection of somatic mosaicism. Compared to Sanger sequencing, which represents a cumulative signal, NGS technology analyzes the sequence of each DNA read in a sample. NGS might therefore facilitate the detection of mosaicism in mothers of MPS II patients. The aim of this study was to reanalyze, by NGS, all MPS II mothers that showed to be non-carriers by Sanger analysis. Twelve non-carriers were selected for the reanalysis on the Ion PGM and Ion Torrent S5 platform, using a custom panel that includes the IDS gene. Results were visualized in the Integrative Genomics Viewer (IGV). We were able to detected the presence of the variant previously found in the index case in three of the mothers, with frequencies ranging between 13 and 49% of the reads. These results suggest the possibility of mosaicism in the mothers. The use of a more sensitive technology for detecting low-level mosaic mutations is essential for accurate recurrence-risk estimates. In our study, the NGS analysis showed to be an effective methodology to detect the mosaic event.
format	article
author	Alice Brinckmann Oliveira Netto Alice Brinckmann Oliveira Netto Ana Carolina Brusius-Facchin Ana Carolina Brusius-Facchin Ana Carolina Brusius-Facchin Sandra Leistner-Segal Francyne Kubaski Francyne Kubaski Francyne Kubaski Francyne Kubaski Juliana Josahkian Juliana Josahkian Roberto Giugliani Roberto Giugliani Roberto Giugliani Roberto Giugliani
author_facet	Alice Brinckmann Oliveira Netto Alice Brinckmann Oliveira Netto Ana Carolina Brusius-Facchin Ana Carolina Brusius-Facchin Ana Carolina Brusius-Facchin Sandra Leistner-Segal Francyne Kubaski Francyne Kubaski Francyne Kubaski Francyne Kubaski Juliana Josahkian Juliana Josahkian Roberto Giugliani Roberto Giugliani Roberto Giugliani Roberto Giugliani
author_sort	Alice Brinckmann Oliveira Netto
title	Detection of Mosaic Variants in Mothers of MPS II Patients by Next Generation Sequencing
title_short	Detection of Mosaic Variants in Mothers of MPS II Patients by Next Generation Sequencing
title_full	Detection of Mosaic Variants in Mothers of MPS II Patients by Next Generation Sequencing
title_fullStr	Detection of Mosaic Variants in Mothers of MPS II Patients by Next Generation Sequencing
title_full_unstemmed	Detection of Mosaic Variants in Mothers of MPS II Patients by Next Generation Sequencing
title_sort	detection of mosaic variants in mothers of mps ii patients by next generation sequencing
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3b22f180790947778d87aeca9c971d99
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Detection of Mosaic Variants in Mothers of MPS II Patients by Next Generation Sequencing

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