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

Autor: Kurtz J; Division of Personalized Genomic Medicine, Department of Pathology and Cell Biology, Columbia University, 630 W. 168th Street, New York, NY 10032, USA., Fernandes JA Jr; Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA., Mansukhani M; Division of Personalized Genomic Medicine, Department of Pathology and Cell Biology, Columbia University, 630 W. 168th Street, New York, NY 10032, USA., Copeland WC; Mitochondrial DNA Replication Group, Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences (NIEHS), NIH, Research Triangle Park, NC 27709, USA., Naini AB; Division of Personalized Genomic Medicine, Department of Pathology and Cell Biology, Columbia University, 630 W. 168th Street, New York, NY 10032, USA.; Department of Neurology, Columbia University, 630 W. 168th Street, New York, NY 10032, USA.
Jazyk: angličtina
Zdroj: Case reports in genetics [Case Rep Genet] 2021 Nov 05; Vol. 2021, pp. 9969071. Date of Electronic Publication: 2021 Nov 05 (Print Publication: 2021).
DOI: 10.1155/2021/9969071
Abstrakt: 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.
Competing Interests: The authors declare no conflicts of interest.
(Copyright © 2021 Justin Kurtz et al.)
Databáze: MEDLINE
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