Recurrent major depression, ataxia, and cardiomyopathy: association with a novel POLG mutation?
نویسندگان
چکیده
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.
منابع مشابه
Polg and Other Mitochondrial Disease Relevance for Psychiatry
ver the last decade, novel mitochondrial genetic diseases have been identified in which mutations in DNA polymerase γ (POLG [MIM 174763]) gene are involved. POLG1 is the only DNA polymerase in human mitochondria and is essential for mitochondrial (mt) DNA replication and repair. It has to be stressed that functional genetic variants of POLG are present in about 0.5 percent of the normal populat...
متن کاملPathogenicity in POLG syndromes: DNA polymerase gamma pathogenicity prediction server and database
DNA polymerase gamma (POLG) is the replicative polymerase responsible for maintaining mitochondrial DNA (mtDNA). Disorders related to its functionality are a major cause of mitochondrial disease. The clinical spectrum of POLG syndromes includes Alpers-Huttenlocher syndrome (AHS), childhood myocerebrohepatopathy spectrum (MCHS), myoclonic epilepsy myopathy sensory ataxia (MEMSA), the ataxia neur...
متن کاملA Novel Mutation in the Aprataxin (APTX) Gene in an Iranian Individual Suffering Early-Onset Ataxia with Oculomotor Apraxia Type 1(AOA1) Disease
Background: Ataxia with oculomotor apraxia type 1 (AOA1) shows early onset with autosomal recessive inheritance and is caused by a mutation in the aprataxin (APTX) gene encoding for the APTX protein. Methods: In this study, a 7-year-old girl born of a first-cousin consanguineous marriage was described with early-onset progressive ataxia and AOA, with increased cholesterol concentration and decr...
متن کاملHereditary Ataxia with a Novel Mutation in the Senataxin Gene: A Case Report
Hereditary ataxias (HA) are a group of inherited neurological disorders caused by changes in genes. At least 115 different mutations in the senataxin (SETX) gene causing ataxia have been identified. There are no reports of any SETX gene mutation among the Iranian population. Here we report on two cases with homozygous and heterozygous mutations in which one patient was affected by HA with oculo...
متن کامل