[Mitochondrial DNA depletion and POLG mutations in a patient with sensory ataxia, dysarthria and ophthalmoplegia].
OBJECTIVE
A broad spectrum of clinical disorders is produced by mutations in the DNA polymerase gamma mitochondrial (POLG) gene which are associated with altered mitochondrial DNA (mtDNA) integrity. The majority of disorders characterized by multiple mtDNA deletions present with progressive external ophthalmoplegia, though this feature is not usually found in syndromes caused by mtDNA depletion. We report on a patient having the clinical triad of sensory ataxic neuropathy, dysarthria and ophthalmoplegia (SANDO), POLG mutations and reduced muscle mtDNA content.


METHODS
The patient presented with sensory ataxic neuropathy, dysarthria and ophthalmoplegia. Diagnosis was established by using histological and genetic procedures (nerve biopsy, mtDNA molecular analysis in skeletal muscle and mutation screening in the POLG gene).


RESULTS
Sural nerve biopsy showed marked loss of large myelinated fibers. Skeletal muscle analysis revealed multiple mtDNA deletions, a marked decrease in mtDNA copy number and pathogenic mutations in the POLG gene.


CONCLUSIONS
POLG mutations must be considered in all patients with the cardinal findings of the SANDO phenotype, without taking into account the type of abnormalities encountered in the mitochondrial genome.
Posada
Ignacio J
IJ
Servicio de Neurología, Hospital Universitario 12 de Octubre, Madrid, España.
Gallardo
María Esther
ME
Domínguez
Cristina
C
Rivera
Henry
H
Cabello
Ana
A
Arenas
Joaquín
J
Martín
Miguel A
MA
Garesse
Rafael
R
Bornstein
Belén
B
D001259:Ataxia / Q000235:genetics*; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004401:Dysarthria / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009886:Ophthalmoplegia / Q000235:genetics*; D010375:Pedigree
D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human