Cargando…

Molecular diagnosis of McArdle disease using whole-exome sequencing

Whole-exome sequencing (WES) analysis has been used recently as a diagnostic tool for finding molecular defects. In the present study, researchers attempted to analyze molecular defects through WES in a 13-year-old female patient who had not been diagnosed through a conventional genetic approach. DN...

Descripción completa

Detalles Bibliográficos
Autores principales: Kang, Ju-Hyung, Park, Jun-Hyung, Park, Jin-Soon, Lee, Seong-Kyu, Lee, Sunghoon, Baik, Haing-Woon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343624/
https://www.ncbi.nlm.nih.gov/pubmed/34373715
http://dx.doi.org/10.3892/etm.2021.10461
_version_ 1783734326006906880
author Kang, Ju-Hyung
Park, Jun-Hyung
Park, Jin-Soon
Lee, Seong-Kyu
Lee, Sunghoon
Baik, Haing-Woon
author_facet Kang, Ju-Hyung
Park, Jun-Hyung
Park, Jin-Soon
Lee, Seong-Kyu
Lee, Sunghoon
Baik, Haing-Woon
author_sort Kang, Ju-Hyung
collection PubMed
description Whole-exome sequencing (WES) analysis has been used recently as a diagnostic tool for finding molecular defects. In the present study, researchers attempted to analyze molecular defects through WES in a 13-year-old female patient who had not been diagnosed through a conventional genetic approach. DNA was extracted and subjected to WES analysis to identify the genetic defect. A total of 106,728 exons and splicing variants were selected, and synonymous single nucleotide variants (SNVs) and general single nucleotide polymorphisms (SNPs) were filtered out. Finally, nonsynonymous SNVs (c.C415T and c.C389T) of the PYGM gene were identified in nine compound heterozygous mutations. PYGM encodes myophosphorylase and degrades glycogen in the muscle to supply energy to muscle cells. The present study revealed that the patient's father had a c.C389T mutation and the mother had a c.C415T mutation, resulting in A130V and R139W missense mutations, respectively. To the best of our knowledge, the A130V variant in PYGM has not been reported in the common variant databases. All variations of the patient's family detected using WES were verified by Sanger sequencing. Because the patient had compound heterozygous mutations in the PYGM gene, the patient was presumed to exhibit markedly decreased muscle phosphorylase activity. To assess the function of myophosphorylase, an ischemic forearm exercise test was performed. The blood ammonia level sharply increased and the lactate level maintained a flat curve shape similar to the typical pattern of McArdle disease. Therefore, the diagnosis of the patient was confirmed to be McArdle disease, a glycogen storage disease. Through WES analysis, accurate and early diagnosis could be made in the present study. This report describes a novel compound heterozygous mutation of the PYGM gene in a Korean patient.
format Online
Article
Text
id pubmed-8343624
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-83436242021-08-08 Molecular diagnosis of McArdle disease using whole-exome sequencing Kang, Ju-Hyung Park, Jun-Hyung Park, Jin-Soon Lee, Seong-Kyu Lee, Sunghoon Baik, Haing-Woon Exp Ther Med Articles Whole-exome sequencing (WES) analysis has been used recently as a diagnostic tool for finding molecular defects. In the present study, researchers attempted to analyze molecular defects through WES in a 13-year-old female patient who had not been diagnosed through a conventional genetic approach. DNA was extracted and subjected to WES analysis to identify the genetic defect. A total of 106,728 exons and splicing variants were selected, and synonymous single nucleotide variants (SNVs) and general single nucleotide polymorphisms (SNPs) were filtered out. Finally, nonsynonymous SNVs (c.C415T and c.C389T) of the PYGM gene were identified in nine compound heterozygous mutations. PYGM encodes myophosphorylase and degrades glycogen in the muscle to supply energy to muscle cells. The present study revealed that the patient's father had a c.C389T mutation and the mother had a c.C415T mutation, resulting in A130V and R139W missense mutations, respectively. To the best of our knowledge, the A130V variant in PYGM has not been reported in the common variant databases. All variations of the patient's family detected using WES were verified by Sanger sequencing. Because the patient had compound heterozygous mutations in the PYGM gene, the patient was presumed to exhibit markedly decreased muscle phosphorylase activity. To assess the function of myophosphorylase, an ischemic forearm exercise test was performed. The blood ammonia level sharply increased and the lactate level maintained a flat curve shape similar to the typical pattern of McArdle disease. Therefore, the diagnosis of the patient was confirmed to be McArdle disease, a glycogen storage disease. Through WES analysis, accurate and early diagnosis could be made in the present study. This report describes a novel compound heterozygous mutation of the PYGM gene in a Korean patient. D.A. Spandidos 2021-09 2021-07-18 /pmc/articles/PMC8343624/ /pubmed/34373715 http://dx.doi.org/10.3892/etm.2021.10461 Text en Copyright: © Kang et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Kang, Ju-Hyung
Park, Jun-Hyung
Park, Jin-Soon
Lee, Seong-Kyu
Lee, Sunghoon
Baik, Haing-Woon
Molecular diagnosis of McArdle disease using whole-exome sequencing
title Molecular diagnosis of McArdle disease using whole-exome sequencing
title_full Molecular diagnosis of McArdle disease using whole-exome sequencing
title_fullStr Molecular diagnosis of McArdle disease using whole-exome sequencing
title_full_unstemmed Molecular diagnosis of McArdle disease using whole-exome sequencing
title_short Molecular diagnosis of McArdle disease using whole-exome sequencing
title_sort molecular diagnosis of mcardle disease using whole-exome sequencing
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343624/
https://www.ncbi.nlm.nih.gov/pubmed/34373715
http://dx.doi.org/10.3892/etm.2021.10461
work_keys_str_mv AT kangjuhyung moleculardiagnosisofmcardlediseaseusingwholeexomesequencing
AT parkjunhyung moleculardiagnosisofmcardlediseaseusingwholeexomesequencing
AT parkjinsoon moleculardiagnosisofmcardlediseaseusingwholeexomesequencing
AT leeseongkyu moleculardiagnosisofmcardlediseaseusingwholeexomesequencing
AT leesunghoon moleculardiagnosisofmcardlediseaseusingwholeexomesequencing
AT baikhaingwoon moleculardiagnosisofmcardlediseaseusingwholeexomesequencing