• Carla Giordano, Floriana Pichiorri, Emma L Blakely, Elena Perli, Maurizia Orlandi, Pietro Gallo, Robert W Taylor, Maurizio Inghilleri, and Giulia d'Amati.
• Department of Experimental Pathology, Sapienza University, Policlinico Umberto I, Roma, Italy.
• Arch. Neurol. 2010 Sep 1;67(9):1144-6.

ObjectiveTo describe an unusual clinical phenotype in an adult harboring 2 compound heterozygous polymerase γ (POLG) mutations.DesignCase report.SettingUniversity-based outpatient neurology clinic and pathology and genetics laboratory.PatientA 27-year-old man presenting with isolated distal myopathy of the upper extremities in the absence of sensory disturbances.ResultsHistochemical 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.ConclusionOur case broadens the phenotypic spectrum of disorders associated with POLG mutations and highlights the complex relationship between genotype and phenotype in POLG-related disease.

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