Recurrent major depression, ataxia, and cardiomyopathy: association with a novel POLG mutation?

W.m.a. Verhoeven, Jos Egger, Hubertus Petrus Henricus Kremer, Boudewijn De Pont, Carlo Marselis

Research output: Contribution to journalArticle

12 Citations (Scopus)


At present, more than 100 disease mutations in mitochondrial DNA polymerase gamma (POLG) have been indentified that are causally related to an array of neuropsychiatric diseases affecting multiple systems. Both autosomal recessive and autosomal dominant forms can be delineated, the latter being associated with Parkinsonism and depressive or psychotic syndromes. In this report, a middle-aged female patient with recurrent major depression with melancholic features, slowly progressive gait instability, and dilated cardiomyopathy is described. Detailed diagnostic evaluation was performed to elucidate the supposed relationship between ataxia, cardiomyopathy, and major depression with melancholia. After extensive genetic and metabolic investigation, a nucleotide substitution c.2207 A -> G in the POLG gene resulting in amino acid change Asn 736Ser in exon 13 was demonstrated. This mutation was considered to be compatible with a mitochondrial disorder and implicated in the pathophysiology of the neuropsychiatric syndrome. It is concluded that this novel POLG mutation forms the most parsimonious etiological explanation for the here-described combination of ataxia, major depression, and cardiomyopathy. Therefore, in patients with a complex neuropsychiatric presentation, extensive diagnostic analysis is warranted, including the search for mitochondriopathies, in order to avoid unnecessary delay of adequate treatment.
Original languageEnglish
Pages (from-to)293-296
Number of pages4
JournalNeuropsychiatric Disease and Treatment
Publication statusPublished - 2011


  • DNA polymerase gamma
  • mitochondrial disease
  • cerebellar ataxia
  • major depression

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