Mitochondrial DNA deletion mutations in patients with neuropsychiatric symptoms

Kato, Maiko; Nakamura, Masayuki; Ichiba, Mio; Tomiyasu, Akiyuki; Shimo, Hirochika; Higuchi, Itsuro; Ueno, Shu‐ichi; Sano, Akira

doi:10.1016/j.neures.2010.12.013

Cited by 31 publications

(22 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We could not find any pathogenic mutations in other genes known to cause mitochondrial diseases with multiple mtDNA deletions ( POLG1 , POLG2 (MIM 604983), C10orf2 (MIM 606075), SLC25A4 (MIM 103220), OPA1 (MIM 605290), TYMP (MIM 131222) and WFS1 (MIM 606201)) in exome analysis, as was observed in a previous study using Sanger sequencing [4]. Although the mtDNA sequence was not targeted by the SureSelect Human All Exon Kit (Agilent, Santa Clara, CA, USA), 16, 558 of 16, 568 (99.9%) bases in mtDNA were read four or more times due to its higher copy number than nuclear DNA, and no known pathogenic variant was found.…”

Section: Resultssupporting

confidence: 55%

“…Previously, we reported a patient who had been born of a first-cousin marriage and was suspected to be affected by inherited progressive external ophthalmoplegia (PEO) [4]. Inherited PEO is a form of mitochondrial disease that follows either autosomal dominant or recessive forms of inheritance (adPEO (MIM 157640; 609283; 609286; 610131, 613077) or arPEO (MIM 258450)).…”

Section: Introductionmentioning

confidence: 99%

“…However, no pathogenic variant in POLG1 (MIM 174763), which encodes a mitochondrial DNA polymerase and was the only established gene whose variants were known to cause arPEO so far, was identified [4]. …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia

et al. 2011

Self Cite

View full text Add to dashboard Cite

BackgroundWhole-exome sequencing using next-generation technologies has been previously demonstrated to be able to detect rare disease-causing variants. Progressive external ophthalmoplegia (PEO) is an inherited mitochondrial disease that follows either autosomal dominant or recessive forms of inheritance (adPEO or arPEO). AdPEO is a genetically heterogeneous disease and several genes, including POLG1 and C10orf2/Twinkle, have been identified as responsible genes. On the other hand, POLG1 was the only established gene causing arPEO with mitochondrial DNA deletions. We previously reported a case of PEO with unidentified genetic etiology. The patient was born of a first-cousin marriage. Therefore, the recessive form of inheritance was suspected.ResultsTo identify the disease-causing variant in this patient, we subjected the patient's DNA to whole-exome sequencing and narrowed down the candidate variants using public data and runs of homozygosity analysis. A total of 35 novel, putatively functional variants were detected in the homozygous segments. When we sorted these variants by the conservation score, a novel missense variant in RRM2B, whose heterozygous rare variant had been known to cause adPEO, was ranked at the top. The list of novel, putatively functional variants did not contain any other variant in genes encoding mitochondrial proteins registered in MitoCarta.ConclusionsExome sequencing efficiently and effectively identified a novel, homozygous missense variant in RRM2B, which was strongly suggested to be causative for arPEO. The findings in this study indicate arPEO to be a genetically heterogeneous disorder, as is the case for adPEO.

show abstract

Section: Resultssupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several reports have demonstrated the existence of mtDNA mutations in patients with psychiatric disorders such as depression, bipolar disorder, schizophrenia, mental retardation, and Asperger syndrome (Fattal et al, 2006;Kato et al, 2011;Munakata et al, 2007;Rollins et al, 2009;Rossignol and Frye, 2012). In the present study, we identified heteroplasmic m.1624C>T mutation in the proband and his mother, who both suffered from neuropsychiatric symptoms including repeated episodes of consciousness disturbance and psychomotor agitation with elevation of lactate and pyruvate in the CSF.…”

Section: Discussionsupporting

confidence: 56%

Heteroplasmic m.1624C>T mutation of the mitochondrial tRNAVal gene in a proband and his mother with repeated consciousness disturbances

et al. 2012

Self Cite

View full text Add to dashboard Cite

“…Besides the muscle biopsy took a more direct approach, showing the decrease of mitochondrial adenosine triphosphate production rate (MAPR) and enzyme ratio in the MDD patient in comparison with controls [15]. In addition, patients with depressive disorder were reported to have more mitochondrial DNA (mtDNA) deletion mutations than controls [15], [16] or share the same mtDNA mutation with mitochondrial diseases [5], [17]–[19]. Last but not least, there were some studies that show “matrilineal inheritance” in some depression affected families.…”

Section: Introductionmentioning

confidence: 99%

Leukocyte Mitochondrial DNA Copy Number in Blood Is Not Associated with Major Depressive Disorder in Young Adults

Tang

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

BackgroundMajor depressive disorder (MDD) is the leading cause of disability worldwide, and has significant genetic predisposition. Mitochondria may have a role in MDD and so mitochondrial DNA (mtDNA) has been suggested as a possible biomarker for this disease. We aimed to test whether the mtDNA copy number of peripheral blood leukocytes is related to MDD in young adults.MethodsA case-control study was conducted with 210 MDD patients and 217 healthy controls (HC). The mtDNA copy number was measured by quantitative polymerase chain reaction (qPCR) method. Depression severity was assessed by the Hamilton-17 Depression Rating Scale (HDRS-17).ResultsWe found no significant differences in mtDNA copy number between MDD patients and HC, though the power analysis showed that our sample size has enough power to detect the difference. There were also no significant correlations between mtDNA copy number and the clinical characteristics (such as age, age of onset, episodes, Hamilton Depression Rating Scale (HDRS) score and Global Assessment of Function Scale (GAF) score) in MDD patients.ConclusionOur study suggests that leukocyte mtDNA copy number is unlikely to contribute to MDD, but it doesn’t mean that we can exclude the possibility of involvement of mitochondria in the disease. Further studies are required to elucidate whether mtDNA can be a biomarker of MDD.

show abstract

Mitochondrial DNA deletion mutations in patients with neuropsychiatric symptoms

Cited by 31 publications

References 27 publications

Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia

Exome sequencing identifies a novel missense variant in RRM2B associated with autosomal recessive progressive external ophthalmoplegia

Heteroplasmic m.1624C>T mutation of the mitochondrial tRNAVal gene in a proband and his mother with repeated consciousness disturbances

Leukocyte Mitochondrial DNA Copy Number in Blood Is Not Associated with Major Depressive Disorder in Young Adults

Contact Info

Product

Resources

About