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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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Autores principales: Eghbali, Maryam, Fatemi, Kiyana Sadat, Salehpour, Shadab, Abiri, Maryam, Saei, Hassan, Talebi, Saeed, Olyaei, Nasrin Alipour, Yassaee, Vahid Reza, Modarressi, Mohammad Hossein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831547/
https://www.ncbi.nlm.nih.gov/pubmed/33505429
http://dx.doi.org/10.3389/fgene.2020.601566
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author Eghbali, Maryam
Fatemi, Kiyana Sadat
Salehpour, Shadab
Abiri, Maryam
Saei, Hassan
Talebi, Saeed
Olyaei, Nasrin Alipour
Yassaee, Vahid Reza
Modarressi, Mohammad Hossein
author_facet Eghbali, Maryam
Fatemi, Kiyana Sadat
Salehpour, Shadab
Abiri, Maryam
Saei, Hassan
Talebi, Saeed
Olyaei, Nasrin Alipour
Yassaee, Vahid Reza
Modarressi, Mohammad Hossein
author_sort Eghbali, Maryam
collection PubMed
description 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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spelling pubmed-78315472021-01-26 Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome Eghbali, Maryam Fatemi, Kiyana Sadat Salehpour, Shadab Abiri, Maryam Saei, Hassan Talebi, Saeed Olyaei, Nasrin Alipour Yassaee, Vahid Reza Modarressi, Mohammad Hossein Front Genet Genetics 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. Frontiers Media S.A. 2021-01-11 /pmc/articles/PMC7831547/ /pubmed/33505429 http://dx.doi.org/10.3389/fgene.2020.601566 Text en Copyright © 2021 Eghbali, Fatemi, Salehpour, Abiri, Saei, Talebi, Olyaei, Yassaee and Modarressi. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Eghbali, Maryam
Fatemi, Kiyana Sadat
Salehpour, Shadab
Abiri, Maryam
Saei, Hassan
Talebi, Saeed
Olyaei, Nasrin Alipour
Yassaee, Vahid Reza
Modarressi, Mohammad Hossein
Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome
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
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
title_fullStr Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome
title_full_unstemmed Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type VI and Fanconi−Bickel Syndrome
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
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
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831547/
https://www.ncbi.nlm.nih.gov/pubmed/33505429
http://dx.doi.org/10.3389/fgene.2020.601566
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