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Mol Genet Metab. 2018 Jun;124(2):124-130. doi: 10.1016/j.ymgme.2018.04.012. Epub 2018 Apr 28.

Clinical and molecular spectrum of thymidine kinase 2-related mtDNA maintenance defect.

Author information

1
Medical Scientist Training Program, Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States. Electronic address: julia.wang@bcm.edu.
2
Department of BioSciences, Rice University, 6100 Main Street, Houston, TX 77005, United States.
3
Department of Human and Molecular Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States.
4
UAMS College of Medicine, Arkansas Children's Hospital, 1 Children's Way, Little Rock, AR 72202, United States.
5
Pathology, Stanford University School of Medicine, R241 Edwards Building, 300 Pasteur Drive, Palo Alto, CA 94305, United States.
6
Division of Clinical Genetics and Metabolic Disorders, Pediatrics Department, Tawam Hospital, Al-Ain, United Arab Emirates.
7
Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, 601 Children's Lane, Norfolk, VA 23507, United States.
8
Department of Pediatric, Neurology and Neurotherapeutics, Children's Health Dallas, University of Texas Southwestern, 2350 N Stemmons Freeway, Dallas, TX 75207, United States.
9
Department of Neurology, Phoenix Children's Hospital, Barrows Neurological Institute, 1919 East Thomas Road, Phoenix, AZ 85016, United States.
10
Genomics Medicine Program, Children's Hospital Minnesota, 2525 Chicago Ave S, Minneapolis, MN 55404, United States.
11
Department of Human and Molecular Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States. Electronic address: ljwong@bcm.edu.

Abstract

Mitochondrial DNA maintenance (mtDNA) defects have a wide range of causes, each with a set of phenotypes that overlap with many other neurological or muscular diseases. Clinicians face the challenge of narrowing down a long list of differential diagnosis when encountered with non-specific neuromuscular symptoms. Biallelic pathogenic variants in the Thymidine Kinase 2 (TK2) gene cause a myopathic form of mitochondrial DNA maintenance defect. Since the first description in 2001, there have been 71 patients reported with 42 unique pathogenic variants. Here we are reporting 11 new cases with 5 novel pathogenic variants. We describe and analyze a total of 82 cases with 47 unique TK2 pathogenic variants in effort to formulate a comprehensive molecular and clinical spectrum of TK2-related mtDNA maintenance disorders.

KEYWORDS:

Adult-onset; Early-onset; Mitochondrial DNA maintenance syndrome; Thymidine kinase 2

PMID:
29735374
DOI:
10.1016/j.ymgme.2018.04.012
[Indexed for MEDLINE]

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