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January 2008

POLG1 Mutations Manifesting as Autosomal Recessive Axonal Charcot-Marie-Tooth Disease

Author Affiliations

Author Affiliations: Departments of Neurology (Drs Harrower, O’Donovan, Findlay, and De Silva) and Neuropathology (Dr O’Donovan), Essex Centre for Neurological Sciences, Queen's Hospital, Romford; Mitochondrial Research Group, The Medical School (Drs Hudson, Taylor, and Chinnery and Ms Stewart), and Institute of Human Genetics (Drs Taylor and Chinnery), Newcastle University, Newcastle upon Tyne; Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London (Dr Houlden); and Department of Neurology, Royal Surrey County Hospital, Guildford (Dr Warner); England.

Arch Neurol. 2008;65(1):133-136. doi:10.1001/archneurol.2007.4

Background  Although a molecular diagnosis is possible in most patients having Charcot-Marie-Tooth disease (CMT), recessively inherited and axonal neuropathies still present a diagnostic challenge.

Objective  To determine the cause of axonal CMT type 2 in 3 siblings.

Design  Case report.

Setting  Academic research.

Participants  Three siblings who subsequently developed profound cerebellar ataxia.

Main Outcome Measures  Muscle biopsy specimen molecular genetic analysis of the POLG1 (polymerase γ-1) gene, as well as screening of control subjects for POLG1 sequence variants.

Results  Cytochrome c oxidase deficient fibers and multiple deletions of mitochondrial DNA were detected in skeletal muscle. Three compound heterozygous substitutions were detected in POLG1.

Conclusion  Even in the absence of classic features of mitochondrial disease, POLG1 should be considered in patients having axonal CMT that may be associated with tremor or ataxia.