title: Exome sequencing identifies a CHKB mutation in Spanish patient with megaconial congenital muscular dystrophy and mtDNA depletion.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Servicio de Neuropediatría, Departamento de Pediatría, Hospital Clínico Universitario, Facultad de Medicina, Santiago de Compostela, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Castro-Gago
authors.affiliation: Servicio de Neuropediatría, Departamento de Pediatría, Hospital Clínico Universitario, Facultad de Medicina, Santiago de Compostela, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Dacruz-Alvarez
authors.affiliation: Servicio de Anatomía Patológica, Hospital Clínico Universitario, Facultad de Medicina, Santiago de Compostela, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Pintos-Martínez
authors.affiliation: Servicio de Anatomía Patológica, Hospital Clínico Universitario, Facultad de Medicina, Santiago de Compostela, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Beiras-Iglesias
authors.affiliation: Laboratorio de Enfermedades Mitocondriales, Instituto de Investigación Hospital 12 de Octubre (i+12), E-28041 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, E-28041 Madrid, Spain.
authors.forename: Aitor
authors.initials: A
authors.lastname: Delmiro
authors.affiliation: Laboratorio de Enfermedades Mitocondriales, Instituto de Investigación Hospital 12 de Octubre (i+12), E-28041 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, E-28041 Madrid, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.affiliation: Laboratorio de Enfermedades Mitocondriales, Instituto de Investigación Hospital 12 de Octubre (i+12), E-28041 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, E-28041 Madrid, Spain.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Martín
authors.affiliation: Laboratorio de Enfermedades Mitocondriales, Instituto de Investigación Hospital 12 de Octubre (i+12), E-28041 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, E-28041 Madrid, Spain. Electronic address: fmartinez@h12o.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez-Azorín
mesh_terms: D002675:Child, Preschool; D002797:Choline Kinase / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D059472:Exome / Q000235:genetics; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications* / Q000235:genetics; D017240:Mitochondrial Myopathies / Q000150:complications* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D013030:Spain
chemical_list: D004272:DNA, Mitochondrial; C542592:CHKB protein, human; D002797:Choline Kinase
keywords: CHKB; Megaconial Congenital Muscular Dystrophy; Mitochondria; Whole-exome sequencing; mtDNA depletion