title: Isolated distal myopathy of the upper limbs associated with mitochondrial DNA depletion and polymerase gamma mutations.
abstract: OBJECTIVE
  To describe an unusual clinical phenotype in an adult harboring 2 compound heterozygous polymerase γ (POLG) mutations.
  
  
  METHODS
  Case report.
  
  
  METHODS
  University-based outpatient neurology clinic and pathology and genetics laboratory.
  
  
  METHODS
  A 27-year-old man presenting with isolated distal myopathy of the upper extremities in the absence of sensory disturbances.
  
  
  RESULTS
  Histochemical analysis of a muscle biopsy specimen showed numerous cytochrome c oxidase-deficient fibers. Molecular analysis revealed marked depletion of muscle mitochondrial DNA in the absence of multiple mitochondrial DNA deletions. Sequence analysis of the POLG gene revealed heterozygous sequence variants in compound c.1156C>T (p.R386C) and c.2794C>T (p.H932Y) segregating with clinical disease in the family. The p.R386C change appears to be a novel mutation.
  
  
  CONCLUSIONS
  Our case broadens the phenotypic spectrum of disorders associated with POLG mutations and highlights the complex relationship between genotype and phenotype in POLG-related disease.
authors.affiliation: Department of Experimental Pathology, Sapienza University, Policlinico Umberto I, Roma, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Giordano
authors.forename: Floriana
authors.initials: F
authors.lastname: Pichiorri
authors.forename: Emma L
authors.initials: EL
authors.lastname: Blakely
authors.forename: Elena
authors.initials: E
authors.lastname: Perli
authors.forename: Maurizia
authors.initials: M
authors.lastname: Orlandi
authors.forename: Pietro
authors.initials: P
authors.lastname: Gallo
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Maurizio
authors.initials: M
authors.lastname: Inghilleri
authors.forename: Giulia
authors.initials: G
authors.lastname: d'Amati
mesh_terms: D000328:Adult; D001132:Arm; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D049310:Distal Myopathies / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human