POLG1 variations presenting as multiple sclerosis.
OBJECTIVE
To describe 2 unrelated patients with novel variations in the POLG1 gene and features undistinguishable from multiple sclerosis, ie, optic neuritis, brain white matter hyperintense areas, and unmatched cerebrospinal fluid oligoclonal bands.


METHODS
Case report.


METHODS
University hospital. Patients  Both patients subsequently developed bilateral ophthalmoplegia, ptosis, myopathy, cardiomyopathy, ataxia, dysphagia, and hearing and cognitive impairment.


METHODS
Detailed clinical and laboratory examinations including brain magnetic resonance imaging, morphological analysis of a muscle biopsy, characterization of mitochondrial DNA integrity, sequencing of the POLG1 gene, and screening of control subjects for POLG1 sequence variants.


RESULTS
Ragged red fibers and multiple deletions of mitochondrial DNA were detected in the skeletal muscle. Four compound heterozygous variations, including 3 previously unreported, were identified in POLG1.


CONCLUSIONS
Clinicians should be aware of the existence of POLG1-related multiple sclerosis-like illness, as it has important implications for management, treatment, and genetic counseling.
Echaniz-Laguna
Andoni
A
Département de Neurologie, Hôpital Civil, 67091 Strasbourg, France. andoni.echaniz-laguna@chru-strasbourg.fr
Chassagne
Maïté
M
de Sèze
Jérôme
J
Mohr
Michel
M
Clerc-Renaud
Pascale
P
Tranchant
Christine
C
Mousson de Camaret
Bénédicte
B
D000328:Adult; D001921:Brain / Q000473:pathology*; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009154:Mutation
D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human