J Clin Neurol.  2011 Mar;7(1):25-30. 10.3988/jcn.2011.7.1.25.

SLC25A4 and C10ORF2 Mutations in Autosomal Dominant Progressive External Ophthalmoplegia

Affiliations
  • 1Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, Korea. dskim@pusan.ac.kr
  • 2Medical Research Institute, Pusan National University School of Medicine, Yangsan, Korea.
  • 3Department of Neurology, Pusan National Univerdity Hospital, Busan, Korea.
  • 4Department of Pathology, Pusan National Univerdity Hospital, Busan, Korea.

Abstract

BACKGROUND
AND PURPOSE: Progressive external ophthalmoplegia (PEO) with Mendelian inheritance is a heterogeneous group of diseases associated with multiple deletions of mitochondrial DNA (mtDNA), which results from the disturbed replication and maintenance of mtDNA secondary to the mutations of nuclear genes including POLG, SLC25A4, C10ORF2, POLG2, OPA1, and RRM2B. The aim of this study was to identify the genetic defects underlying the pathology and clinical features in two Korean kindreds with autosomal dominant PEO.
METHODS
Two pathologically proven PEO patients with a clear autosomal dominant pattern of inheritance were selected. To exclude a large-scale rearrangement, a long-range polymerase chain reaction (PCR) was performed using DNA extracted from biopsied muscle tissue taken from each patient. All coding regions and exon-intron boundaries of POLG, SLC25A4, C10ORF2, and POLG2 were amplified by PCR and directly sequenced.
RESULTS
One patient showed multiple deletions of mtDNA on long-range PCR analysis, and two known heterozygous missense mutations in SLC25A4 (p.Asp104Gly) and C10ORF2 (p.Glu479Lys) were identified in each patient. The p.Asp104Gly mutation in SLC25A4 was identified in the patient with an early onset, slowly progressive, pure PEO phenotype, while the p.Glu479Lys mutation in C10ORF2 was identified in the other patient, with a late-onset disease and PEO plus phenotype.
CONCLUSIONS
Two mutations affecting nuclear genes were identified in Korean patients with autosomal dominant PEO. Further studies are necessary to identify the clear pathogenetic mechanisms and establish genotype-phenotype correlations in autosomal dominant PEO.

Keyword

autosomal dominant trait; progressive external ophthalmoplegia; mutation; SLC25A4; C10ORF2
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