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September 2010

Isolated Distal Myopathy of the Upper Limbs Associated With Mitochondrial DNA Depletion and Polymerase γ Mutations

Author Affiliations

Author Affiliations: Dipartimento di Medicina Sperimentale (Drs Giordano, Gallo, and d’Amati and Mss Perli and Orlandi), UOC Neurologia B (Drs Pichiorri and Inghilleri), and S. Raffaele Institute, IRCCS (Dr Inghilleri), Sapienza University of Rome, Rome, Italy; and Mitochondrial Research Group and National Commissioning Group Rare Mitochondrial Disorders of Adults and Children Service, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, England (Drs Blakely and Taylor).

Arch Neurol. 2010;67(9):1144-1146. doi:10.1001/archneurol.2010.200

Objective  To describe an unusual clinical phenotype in an adult harboring 2 compound heterozygous polymerase γ (POLG) mutations.

Design  Case report.

Setting  University-based outpatient neurology clinic and pathology and genetics laboratory.

Patient  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.

Conclusion  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.