title: Mitochondrial disorders of DNA polymerase γ dysfunction: from anatomic to molecular pathology diagnosis.
abstract: BACKGROUND
  Primary mitochondrial dysfunction is one of the most common causes of inherited disorders predominantly involving the neuromuscular system. Advances in the molecular study of mitochondrial DNA have changed our vision and our approach to primary mitochondrial disorders. Many of the mitochondrial disorders are caused by mutations in nuclear genes and are inherited in an autosomal recessive pattern. Among the autosomal inherited mitochondrial disorders, those related to DNA polymerase γ dysfunction are the most common and the best studied. Understanding the molecular mechanisms and being familiar with the recent advances in laboratory diagnosis of this group of mitochondrial disorders are essential for pathologists to interpret abnormal histopathology and laboratory results and to suggest further studies for a definitive diagnosis.
  
  
  OBJECTIVE
  To help pathologists better understand the common clinical syndromes originating from mutations in DNA polymerase γ and its associated proteins and use the stepwise approach of clinical, laboratory, and pathologic diagnosis of these syndromes.
  
  
  METHODS
  Review of pertinent published literature and relevant Internet databases.
  
  
  CONCLUSIONS
  Mitochondrial disorders are now better recognized with the development of molecular tests for clinical diagnosis. A cooperative effort among primary physicians, diagnostic pathologists, geneticists, and molecular biologists with expertise in mitochondrial disorders is required to reach a definitive diagnosis.
authors: Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA. zha@musc.edu
authors: Linsheng
authors: L
authors: Zhang
authors: Sherine S L
authors: SS
authors: Chan
authors: Daynna J
authors: DJ
authors: Wolff
mesh_terms: D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D025202:Molecular Diagnostic Techniques
chemical_list: D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase