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

Verhoeven WM, Egger JI, Kremer BP, de Pont BJ, Marcelis CL - Neuropsychiatr Dis Treat (2011)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands;

ABSTRACT
At present, more than 100 disease mutations in mitochondrial DNA polymerase γ (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.

No MeSH data available.


Related in: MedlinePlus

Axial, T2-weighted magnetic resonance image of the patient, showing atrophy of the cerebellum and the cerebellar vermis.
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f1-ndt-7-293: Axial, T2-weighted magnetic resonance image of the patient, showing atrophy of the cerebellum and the cerebellar vermis.

Mentions: Treatment with citalopram in a maximal dose of 20 mg daily resulted in a gradual reduction of depressive symptoms, even though inactivity and loss of energy persisted and cerebellar dysfunctions became more prominent. An MRI (magnetic resonance imaging) scan of the brain demonstrated marked cerebellar atrophy without any supratentorial lesions (Figure 1). Karyotyping revealed no abnormalities.


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

Verhoeven WM, Egger JI, Kremer BP, de Pont BJ, Marcelis CL - Neuropsychiatr Dis Treat (2011)

Axial, T2-weighted magnetic resonance image of the patient, showing atrophy of the cerebellum and the cerebellar vermis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101889&req=5

f1-ndt-7-293: Axial, T2-weighted magnetic resonance image of the patient, showing atrophy of the cerebellum and the cerebellar vermis.
Mentions: Treatment with citalopram in a maximal dose of 20 mg daily resulted in a gradual reduction of depressive symptoms, even though inactivity and loss of energy persisted and cerebellar dysfunctions became more prominent. An MRI (magnetic resonance imaging) scan of the brain demonstrated marked cerebellar atrophy without any supratentorial lesions (Figure 1). Karyotyping revealed no abnormalities.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands;

ABSTRACT
At present, more than 100 disease mutations in mitochondrial DNA polymerase γ (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.

No MeSH data available.


Related in: MedlinePlus