POLG1 mutations manifesting as autosomal recessive axonal Charcot-Marie-Tooth disease.
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.


METHODS
Case report.


METHODS
Academic research.


METHODS
Three siblings who subsequently developed profound cerebellar ataxia.


METHODS
Muscle biopsy specimen molecular genetic analysis of the POLG1 (polymerase gamma-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.


CONCLUSIONS
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.
Harrower
Timothy
T
Department of Neurology, Essex Center for Neurological Sciences, Queen's Hospital, Romford, England.
Stewart
Joanna D
JD
Hudson
Gavin
G
Houlden
Henry
H
Warner
Graham
G
O'Donovan
Dominic G
DG
Findlay
Leslie J
LJ
Taylor
Robert W
RW
De Silva
Rajith
R
Chinnery
Patrick F
PF
D000328:Adult; D019943:Amino Acid Substitution; D001369:Axons / Q000473:pathology*; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D020732:Cytogenetic Analysis; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics; D005190:Family; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000473:pathology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009460:Neurologic Examination; D010375:Pedigree; D017933:Peripheral Nervous System / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013132:Spinocerebellar Degenerations / Q000175:diagnosis / Q000235:genetics / Q000473:pathology
D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human