POLG1 Mutations Manifesting as Autosomal Recessive Axonal CMT

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POLG1 Mutations Manifesting as Autosomal Recessive Axonal Charcot-

Marie-Tooth Disease

Harrower, MRCP; Joanna D. , BSc; Gavin Hudson, PhD;

Henry Houlden, MRCP(UK); Graham Warner, MRCP; Dominic G. O'Donovan,

FRCPath; J. Findlay, FRCP; W. , PhD; Rajith De

Silva, FRCP; F. Chinnery, PhD, FRCP

Arch Neurol. 2008;65(1):133-136.

http://archneur.ama-assn.org/cgi/content/short/65/1/133

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 -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.

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,

, and Chinnery and Ms ), and Institute of Human

Genetics (Drs 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.