Whole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion

Mitochondrial DNA (mtDNA) depletion syndromes are a group of autosomal recessive disorders associated with a spectrum of clinical diseases, which include progressive external ophthalmoplegia (PEO). They are caused by variants in nuclear DNA (nDNA) encoded genes, and the gene that encodes for mtDNA p...

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Autores principales:	Justin Kurtz, Joseph Americo Fernandes, Mahesh Mansukhani, William C. Copeland, Ali B. Naini
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/530aba970bae4c4f8bde706d79e970eb
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spelling	oai:doaj.org-article:530aba970bae4c4f8bde706d79e970eb2021-11-15T01:19:35ZWhole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion2090-655210.1155/2021/9969071https://doaj.org/article/530aba970bae4c4f8bde706d79e970eb2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/9969071https://doaj.org/toc/2090-6552Mitochondrial DNA (mtDNA) depletion syndromes are a group of autosomal recessive disorders associated with a spectrum of clinical diseases, which include progressive external ophthalmoplegia (PEO). They are caused by variants in nuclear DNA (nDNA) encoded genes, and the gene that encodes for mtDNA polymerase gamma (POLG) is commonly involved. A splice-site mutation in POLG, c.3104+3A > T, was previously identified in three families with findings of PEO, and studies demonstrated this variant to result in skipping of exon 19. Here, we report a 57-year-old female who presented with ophthalmoplegia, ptosis, muscle weakness, and exercise intolerance with a subsequent muscle biopsy demonstrating mitochondrial myopathy on histopathologic evaluation and multiple mtDNA deletions by southern blot analysis. Whole-exome sequencing identified the previously characterized c. 3104+3A > T splice-site mutation in compound heterozygosity with a novel frameshift variant, p.Gly23Serfs∗236 (c.67_88del). mtDNA copy number analysis performed on the patient’s muscle showed mtDNA depletion, as expected in a patient with biallelic pathogenic mutations in POLG. This is the first reported case with POLG p.Gly23Serfs∗236, discovered in a patient presenting with features of PEO.Justin KurtzJoseph Americo FernandesMahesh MansukhaniWilliam C. CopelandAli B. NainiHindawi LimitedarticleGeneticsQH426-470ENCase Reports in Genetics, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Justin Kurtz Joseph Americo Fernandes Mahesh Mansukhani William C. Copeland Ali B. Naini Whole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion
description	Mitochondrial DNA (mtDNA) depletion syndromes are a group of autosomal recessive disorders associated with a spectrum of clinical diseases, which include progressive external ophthalmoplegia (PEO). They are caused by variants in nuclear DNA (nDNA) encoded genes, and the gene that encodes for mtDNA polymerase gamma (POLG) is commonly involved. A splice-site mutation in POLG, c.3104+3A > T, was previously identified in three families with findings of PEO, and studies demonstrated this variant to result in skipping of exon 19. Here, we report a 57-year-old female who presented with ophthalmoplegia, ptosis, muscle weakness, and exercise intolerance with a subsequent muscle biopsy demonstrating mitochondrial myopathy on histopathologic evaluation and multiple mtDNA deletions by southern blot analysis. Whole-exome sequencing identified the previously characterized c. 3104+3A > T splice-site mutation in compound heterozygosity with a novel frameshift variant, p.Gly23Serfs∗236 (c.67_88del). mtDNA copy number analysis performed on the patient’s muscle showed mtDNA depletion, as expected in a patient with biallelic pathogenic mutations in POLG. This is the first reported case with POLG p.Gly23Serfs∗236, discovered in a patient presenting with features of PEO.
format	article
author	Justin Kurtz Joseph Americo Fernandes Mahesh Mansukhani William C. Copeland Ali B. Naini
author_facet	Justin Kurtz Joseph Americo Fernandes Mahesh Mansukhani William C. Copeland Ali B. Naini
author_sort	Justin Kurtz
title	Whole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion
title_short	Whole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion
title_full	Whole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion
title_fullStr	Whole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion
title_full_unstemmed	Whole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion
title_sort	whole-exome sequencing identifies a novel polg frameshift variant in an adult patient presenting with progressive external ophthalmoplegia and mitochondrial dna depletion
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/530aba970bae4c4f8bde706d79e970eb
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Whole-Exome Sequencing Identifies a Novel POLG Frameshift Variant in an Adult Patient Presenting with Progressive External Ophthalmoplegia and Mitochondrial DNA Depletion

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