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Exome sequencing identifies a CHKB mutation in Spanish patient with Megaconial Congenital Muscular Dystrophy and mtDNA depletion.

Authors :
Castro-Gago, Manuel
Dacruz-Alvarez, David
Pintos-Martínez, Elena
Beiras-Iglesias, Andrés
Delmiro, Aitor
Arenas, Joaquín
Martín, Miguel Ángel
Martínez-Azorín, Francisco
Source :
European Journal of Paediatric Neurology; Nov2014, Vol. 18 Issue 6, p796-800, 5p
Publication Year :
2014

Abstract

Background Choline kinase beta gene ( CHKB ) mutations have been identified in Megaconial Congenital Muscular Dystrophy (MDCMC) patients, but never in patients with an additional combined deficiency of complexes I, III and IV and mitochondrial DNA (mtDNA) depletion. 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10903798
Volume :
18
Issue :
6
Database :
Supplemental Index
Journal :
European Journal of Paediatric Neurology
Publication Type :
Academic Journal
Accession number :
99069207
Full Text :
https://doi.org/10.1016/j.ejpn.2014.06.005