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Neuromuscul Disord. 2018 Feb;28(2):137-143. doi: 10.1016/j.nmd.2017.10.006. Epub 2017 Oct 31.

Identification and characterization of the novel m.8305C>T MTTK and m.4440G>A MTTM gene mutations causing mitochondrial myopathies.

Author information

1
Section of Neurology, Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy.
2
Mitochondrial Disorders Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
3
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain; Laboratori de Malalties Neuromusculars, Institut de Recerca Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.
4
Unidad de Metabolopatías, Servicio de Bioquímica, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
5
Department of Neurosciences and Department of Onco-Haematology, University Hospitals of Modena & Reggio Emilia, Italy.
6
Division of Neurology, Department of Neuroscience, Azienda Ospedaliero Universitaria, Udine, Italy.
7
Mitochondrial Disorders Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain; Àrea de Genètica Clínica i Molecular, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Electronic address: elena.garcia@vhir.org.
8
Mitochondrial Disorders Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. Electronic address: tomas.pinos@vhir.org.

Abstract

We report on two novel mtDNA mutations in patients affected with mitochondrial myopathy. The first patient, a 44-year-old woman, had bilateral eyelid ptosis and the m.8305C>T mutation in the MTTK gene. The second patient, a 56-year-old man, had four-limb muscle weakness and the MTTM gene m.4440G>A mutation. Muscle biopsies in both patients showed ragged red fibers and numerous COX-negative fibers as well as a combined defect of complex I, III and IV activities. The two mutations were heteroplasmic and detected only in muscle tissue, with a higher mutation load in COX-negative fibers. Additionally, both mutations occurred in highly conserved mt-tRNA sites, and were not found by an in silico search in 30,589 human mtDNA sequences. Our report further expands the mutational and phenotypic spectrum of diseases associated with mutations in mitochondrial tRNA genes and reinforces the notion that mutations in mitochondrial tRNAs represent hot spots for mitochondrial myopathies in adults.

KEYWORDS:

Mitochondrial diseases; Myopathy; PEO; mtDNA

PMID:
29174468
DOI:
10.1016/j.nmd.2017.10.006

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