title: Novel CHKB mutation expands the megaconial muscular dystrophy phenotype.
abstract: BACKGROUND
  Mutations in the choline kinase beta (CHKB) gene are associated with a congenital muscular dystrophy with giant mitochondria at the periphery of muscle fibers.
  
  
  METHODS
  We describe a patient of Italian origin in whom whole-exome sequencing revealed a novel homozygous nonsense mutation, c.648C>A, p.(Tyr216*), in exon 5 of CHKB.
  
  
  RESULTS
  The patient presented with limb-girdle weakness and hypotonia from birth with mental retardation, and had sudden and transient deteriorations of muscle strength with acute intercurrent illnesses. Previously undescribed sarcolemmal overexpression of utrophin was noted in the muscle biopsy.
  
  
  CONCLUSIONS
  Pathological features broaden the description of the entity and provide new insight in the pathogenic mechanisms. This case highlights the usefulness of next-generation sequencing in the diagnosis of rare and incompletely understood conditions.
authors.affiliation: Centre for Medical Research, University of Western Australia, Harry Perkins Institute of Medical Research, QQ Block, QEII Medical Centre, 6 Verdun Street, Perth, Western Australia, 6009, Australia; Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Macarena
authors.initials: M
authors.lastname: Cabrera-Serrano
authors.forename: Reimar C
authors.initials: RC
authors.lastname: Junckerstorff
authors.forename: Vanessa
authors.initials: V
authors.lastname: Atkinson
authors.forename: Padma
authors.initials: P
authors.lastname: Sivadorai
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Allcock
authors.forename: Phillipa
authors.initials: P
authors.lastname: Lamont
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Laing
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002648:Child; D002797:Choline Kinase / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009218:Myosins / Q000378:metabolism; D049411:Utrophin / Q000378:metabolism
chemical_list: D049411:Utrophin; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; C542592:CHKB protein, human; D002797:Choline Kinase; D009218:Myosins
keywords: CHKB; congenital muscular dystrophy; megaconial myopathy; mitochondrial myopathy; utrophin upregulation