Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome

Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WE...
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Autor*in:	Maryam Eghbali [verfasserIn] Kiyana Sadat Fatemi [verfasserIn] Shadab Salehpour [verfasserIn] Maryam Abiri [verfasserIn] Hassan Saei [verfasserIn] Saeed Talebi [verfasserIn] Nasrin Alipour Olyaei [verfasserIn] Vahid Reza Yassaee [verfasserIn] Mohammad Hossein Modarressi [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	glycogen storage diseases whole-exome sequencing novel causative variants secondary/incidental findings pharmacogenetic variants

Übergeordnetes Werk:	In: Frontiers in Genetics - Frontiers Media S.A., 2011, 11(2021)
Übergeordnetes Werk:	volume:11 ; year:2021

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fgene.2020.601566

Katalog-ID:	DOAJ054941369

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520			\|a Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG’s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298_307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG’s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset.
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allfields	10.3389/fgene.2020.601566 doi (DE-627)DOAJ054941369 (DE-599)DOAJd0fbfc0c01d64d0daf92024e91a3ee2a DE-627 ger DE-627 rakwb eng QH426-470 Maryam Eghbali verfasserin aut Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG’s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298_307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG’s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset. glycogen storage diseases whole-exome sequencing novel causative variants secondary/incidental findings pharmacogenetic variants Genetics Kiyana Sadat Fatemi verfasserin aut Shadab Salehpour verfasserin aut Shadab Salehpour verfasserin aut Maryam Abiri verfasserin aut Maryam Abiri verfasserin aut Hassan Saei verfasserin aut Saeed Talebi verfasserin aut Nasrin Alipour Olyaei verfasserin aut Vahid Reza Yassaee verfasserin aut Mohammad Hossein Modarressi verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 11(2021) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:11 year:2021 https://doi.org/10.3389/fgene.2020.601566 kostenfrei https://doaj.org/article/d0fbfc0c01d64d0daf92024e91a3ee2a kostenfrei https://www.frontiersin.org/articles/10.3389/fgene.2020.601566/full kostenfrei https://doaj.org/toc/1664-8021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021
spelling	10.3389/fgene.2020.601566 doi (DE-627)DOAJ054941369 (DE-599)DOAJd0fbfc0c01d64d0daf92024e91a3ee2a DE-627 ger DE-627 rakwb eng QH426-470 Maryam Eghbali verfasserin aut Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG’s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298_307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG’s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset. glycogen storage diseases whole-exome sequencing novel causative variants secondary/incidental findings pharmacogenetic variants Genetics Kiyana Sadat Fatemi verfasserin aut Shadab Salehpour verfasserin aut Shadab Salehpour verfasserin aut Maryam Abiri verfasserin aut Maryam Abiri verfasserin aut Hassan Saei verfasserin aut Saeed Talebi verfasserin aut Nasrin Alipour Olyaei verfasserin aut Vahid Reza Yassaee verfasserin aut Mohammad Hossein Modarressi verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 11(2021) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:11 year:2021 https://doi.org/10.3389/fgene.2020.601566 kostenfrei https://doaj.org/article/d0fbfc0c01d64d0daf92024e91a3ee2a kostenfrei https://www.frontiersin.org/articles/10.3389/fgene.2020.601566/full kostenfrei https://doaj.org/toc/1664-8021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021
allfields_unstemmed	10.3389/fgene.2020.601566 doi (DE-627)DOAJ054941369 (DE-599)DOAJd0fbfc0c01d64d0daf92024e91a3ee2a DE-627 ger DE-627 rakwb eng QH426-470 Maryam Eghbali verfasserin aut Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG’s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298_307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG’s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset. glycogen storage diseases whole-exome sequencing novel causative variants secondary/incidental findings pharmacogenetic variants Genetics Kiyana Sadat Fatemi verfasserin aut Shadab Salehpour verfasserin aut Shadab Salehpour verfasserin aut Maryam Abiri verfasserin aut Maryam Abiri verfasserin aut Hassan Saei verfasserin aut Saeed Talebi verfasserin aut Nasrin Alipour Olyaei verfasserin aut Vahid Reza Yassaee verfasserin aut Mohammad Hossein Modarressi verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 11(2021) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:11 year:2021 https://doi.org/10.3389/fgene.2020.601566 kostenfrei https://doaj.org/article/d0fbfc0c01d64d0daf92024e91a3ee2a kostenfrei https://www.frontiersin.org/articles/10.3389/fgene.2020.601566/full kostenfrei https://doaj.org/toc/1664-8021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021
allfieldsGer	10.3389/fgene.2020.601566 doi (DE-627)DOAJ054941369 (DE-599)DOAJd0fbfc0c01d64d0daf92024e91a3ee2a DE-627 ger DE-627 rakwb eng QH426-470 Maryam Eghbali verfasserin aut Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG’s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298_307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG’s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset. glycogen storage diseases whole-exome sequencing novel causative variants secondary/incidental findings pharmacogenetic variants Genetics Kiyana Sadat Fatemi verfasserin aut Shadab Salehpour verfasserin aut Shadab Salehpour verfasserin aut Maryam Abiri verfasserin aut Maryam Abiri verfasserin aut Hassan Saei verfasserin aut Saeed Talebi verfasserin aut Nasrin Alipour Olyaei verfasserin aut Vahid Reza Yassaee verfasserin aut Mohammad Hossein Modarressi verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 11(2021) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:11 year:2021 https://doi.org/10.3389/fgene.2020.601566 kostenfrei https://doaj.org/article/d0fbfc0c01d64d0daf92024e91a3ee2a kostenfrei https://www.frontiersin.org/articles/10.3389/fgene.2020.601566/full kostenfrei https://doaj.org/toc/1664-8021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021
allfieldsSound	10.3389/fgene.2020.601566 doi (DE-627)DOAJ054941369 (DE-599)DOAJd0fbfc0c01d64d0daf92024e91a3ee2a DE-627 ger DE-627 rakwb eng QH426-470 Maryam Eghbali verfasserin aut Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG’s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298_307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG’s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset. glycogen storage diseases whole-exome sequencing novel causative variants secondary/incidental findings pharmacogenetic variants Genetics Kiyana Sadat Fatemi verfasserin aut Shadab Salehpour verfasserin aut Shadab Salehpour verfasserin aut Maryam Abiri verfasserin aut Maryam Abiri verfasserin aut Hassan Saei verfasserin aut Saeed Talebi verfasserin aut Nasrin Alipour Olyaei verfasserin aut Vahid Reza Yassaee verfasserin aut Mohammad Hossein Modarressi verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 11(2021) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:11 year:2021 https://doi.org/10.3389/fgene.2020.601566 kostenfrei https://doaj.org/article/d0fbfc0c01d64d0daf92024e91a3ee2a kostenfrei https://www.frontiersin.org/articles/10.3389/fgene.2020.601566/full kostenfrei https://doaj.org/toc/1664-8021 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2021
language	English
source	In Frontiers in Genetics 11(2021) volume:11 year:2021
sourceStr	In Frontiers in Genetics 11(2021) volume:11 year:2021
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institution	findex.gbv.de
topic_facet	glycogen storage diseases whole-exome sequencing novel causative variants secondary/incidental findings pharmacogenetic variants Genetics
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container_title	Frontiers in Genetics
authorswithroles_txt_mv	Maryam Eghbali @@aut@@ Kiyana Sadat Fatemi @@aut@@ Shadab Salehpour @@aut@@ Maryam Abiri @@aut@@ Hassan Saei @@aut@@ Saeed Talebi @@aut@@ Nasrin Alipour Olyaei @@aut@@ Vahid Reza Yassaee @@aut@@ Mohammad Hossein Modarressi @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
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topic_title	QH426-470 Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome glycogen storage diseases whole-exome sequencing novel causative variants secondary/incidental findings pharmacogenetic variants
topic	misc QH426-470 misc glycogen storage diseases misc whole-exome sequencing misc novel causative variants misc secondary/incidental findings misc pharmacogenetic variants misc Genetics
topic_unstemmed	misc QH426-470 misc glycogen storage diseases misc whole-exome sequencing misc novel causative variants misc secondary/incidental findings misc pharmacogenetic variants misc Genetics
topic_browse	misc QH426-470 misc glycogen storage diseases misc whole-exome sequencing misc novel causative variants misc secondary/incidental findings misc pharmacogenetic variants misc Genetics
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title	Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome
ctrlnum	(DE-627)DOAJ054941369 (DE-599)DOAJd0fbfc0c01d64d0daf92024e91a3ee2a
title_full	Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome
author_sort	Maryam Eghbali
journal	Frontiers in Genetics
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author_browse	Maryam Eghbali Kiyana Sadat Fatemi Shadab Salehpour Maryam Abiri Hassan Saei Saeed Talebi Nasrin Alipour Olyaei Vahid Reza Yassaee Mohammad Hossein Modarressi
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title_sort	whole-exome sequencing uncovers novel causative variants and additional findings in three patients affected by glycogen storage disease type vi and fanconi−bickel syndrome
callnumber	QH426-470
title_auth	Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome
abstract	Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG’s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298_307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG’s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset.
abstractGer	Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG’s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298_307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG’s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset.
abstract_unstemmed	Glycogen storage diseases (GSDs) are the heterogeneous group of disorders caused by mutations in at least 30 different genes. Different types of GSDs, especially liver GSDs, take overlapping symptoms and can be clinically indistinguishable. This survey evaluated the use of whole-exome sequencing (WES) for the genetic analysis of the liver GSD-suspected patients in three unrelated families. An in-house filtering pipeline was used to assess rare pathogenic variants in GSD-associated genes, autosomal recessive/mendelian disorder genes (carrier status for genetic counseling subjects), and the ACMG’s list of 59 actionable genes. For the interpretation of the causative variants and the incidental/secondary findings, ACMG guidelines were applied. Additionally, we have explored PharmGKB class IA/IB pharmacogenetic variants. The segregation analysis was performed using Sanger sequencing for the novel causative variants. Bioinformatics analysis of the exome data in three individuals revealed three novel homozygous causative variants in the GSD-associated genes. The first variant, c.298_307delATGATCAACC in PYGL gene has related to HERS disease (GSD VI). Both variants of c.1043dupT and c.613-1G > C in SLC2A2 gene have been associated with Fanconi-Bickel syndrome (GSDXI). Eight pathogenic/likely pathogenic medical actionable findings in Mendelian disease genes and 10 pharmacogenetic variants with underlying drug response phenotypes have been identified. No known/expected pathogenic variants were detected in the ACMG’s list of 59 actionable genes. The logical filtering steps can help in finding other medical actionable secondary/incidental findings as well as effectively identifying the causative variants in heterogeneous conditions such as GSDs. Three novel variants related to GSD genes recognized in liver GSD-suspected patients with early infantile and childhood-age onset.
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title_short	Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome
url	https://doi.org/10.3389/fgene.2020.601566 https://doaj.org/article/d0fbfc0c01d64d0daf92024e91a3ee2a https://www.frontiersin.org/articles/10.3389/fgene.2020.601566/full https://doaj.org/toc/1664-8021
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author2	Kiyana Sadat Fatemi Shadab Salehpour Maryam Abiri Hassan Saei Saeed Talebi Nasrin Alipour Olyaei Vahid Reza Yassaee Mohammad Hossein Modarressi
author2Str	Kiyana Sadat Fatemi Shadab Salehpour Maryam Abiri Hassan Saei Saeed Talebi Nasrin Alipour Olyaei Vahid Reza Yassaee Mohammad Hossein Modarressi
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up_date	2024-07-04T01:11:57.359Z
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