Abstract | BACKGROUND: AIMS: To report mutations in carry genes for MDCMC with respiratory chain defects and mtDNA depletion. METHODS: Whole-exome sequencing (WES) was used to identify the carry genes in a Spanish child with muscle weakness, mild hypotonia at lower limb muscles, mildly elevated creatine kinase (CK), enlarged mitochondria in the periphery of the fibers, combined deficiency of complex I, III and IV and depletion of mtDNA. RESULTS: With WES data, it was possible to get the whole mtDNA sequencing and discard any pathogenic variant in this genome. The first filter of WES data with the nuclear-encoded mitochondrial genes (MitoCarta) did not get any candidate. However, the analysis of whole exome uncovered a homozygous nonsense pathogenic mutation in CHKB gene (NM_005198.4:c.810T>A, p.Tyr270*). CONCLUSIONS: Our data confirm the role of CHKB in MDCMC and point to this gene as unique candidate for the combined deficiency of respiratory chain and mtDNA depletion observed in this patient.
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Authors | Manuel Castro-Gago, David Dacruz-Alvarez, Elena Pintos-Martínez, Andrés Beiras-Iglesias, Aitor Delmiro, Joaquín Arenas, Miguel Ángel Martín, Francisco Martínez-Azorín |
Journal | European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
(Eur J Paediatr Neurol)
Vol. 18
Issue 6
Pg. 796-800
(Nov 2014)
ISSN: 1532-2130 [Electronic] England |
PMID | 24997086
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. |
Chemical References |
- DNA, Mitochondrial
- CHKB protein, human
- Choline Kinase
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Topics |
- Child, Preschool
- Choline Kinase
(genetics)
- DNA, Mitochondrial
(genetics)
- Exome
(genetics)
- Humans
- Male
- Metabolism, Inborn Errors
(complications, genetics)
- Mitochondrial Myopathies
(complications, genetics)
- Mutation
(genetics)
- Spain
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