Mitochondrial DNA Mutations in two Bulgarian Children with Autistic Spectrum Disorders

Avdjieva-Tzavella, Daniela; Mihailova, Snezhina; Lukanov, C; Naumova, Elissaveta; Simeonov, E; Tincheva, Radka; Toncheva, Draga

doi:10.2478/bjmg-2013-0006

Cited by 15 publications

(7 citation statements)

References 25 publications

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“…Numerous mtDNA point mutations [ 105 , 106 ] and deletions [ 107 ] show association with ASD; large-scale mtDNA deletions have been associated with epilepsy [ 21 ]. Examples of mtDNA genes reported include MT-ATP6 [ 85 , 108 , 109 ], MT-ND5 [ 108 ], MT-CYB [ 110 ], MT-TK [ 111 ] and MT-TL1 [ 112 ], and MT-CO1 and MT-CO2 [ 113 ]. Mutations in mtDNA such as m.3260A > G that causes mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) have been associated with ASD [ 104 , 112 ], as has primary Leber hereditary optic neuropathy mtDNA mutations [ 104 ].…”

Section: Summary Of the Literaturementioning

confidence: 99%

Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder

Rose

Niyazov

Rossignol³

et al. 2018

Mol Diagn Ther

185

148

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Autism spectrum disorder (ASD) affects ~ 2% of children in the United States. The etiology of ASD likely involves environmental factors triggering physiological abnormalities in genetically sensitive individuals. One of these major physiological abnormalities is mitochondrial dysfunction, which may affect a significant subset of children with ASD. Here we systematically review the literature on human studies of mitochondrial dysfunction related to ASD. Clinical aspects of mitochondrial dysfunction in ASD include unusual neurodevelopmental regression, especially if triggered by an inflammatory event, gastrointestinal symptoms, seizures, motor delays, fatigue and lethargy. Traditional biomarkers of mitochondrial disease are widely reported to be abnormal in ASD, but appear non-specific. Newer biomarkers include buccal cell enzymology, biomarkers of fatty acid metabolism, non-mitochondrial enzyme function, apoptosis markers and mitochondrial antibodies. Many genetic abnormalities are associated with mitochondrial dysfunction in ASD, including chromosomal abnormalities, mitochondrial DNA mutations and large-scale deletions, and mutations in both mitochondrial and non-mitochondrial nuclear genes. Mitochondrial dysfunction has been described in immune and buccal cells, fibroblasts, muscle and gastrointestinal tissue and the brains of individuals with ASD. Several environmental factors, including toxicants, microbiome metabolites and an oxidized microenvironment are shown to modulate mitochondrial function in ASD tissues. Investigations of treatments for mitochondrial dysfunction in ASD are promising but preliminary. The etiology of mitochondrial dysfunction and how to define it in ASD is currently unclear. However, preliminary evidence suggests that the mitochondria may be a fruitful target for treatment and prevention of ASD. Further research is needed to better understand the role of mitochondrial dysfunction in the pathophysiology of ASD.

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Section: Summary Of the Literaturementioning

confidence: 99%

Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder

Rose

Niyazov

Rossignol³

et al. 2018

Mol Diagn Ther

185

148

View full text Add to dashboard Cite

show abstract

“…This variant is located in a protected area which has a destructive effect on the protein structure [29]. Overall G9055A variant has been reported in a few studies but merely as a simple report, without detailed assessment of its association with autism [1]. But, regarding previous related studies we find a correlation between this variant and amyloidosis and a correlation between amyloidosis and autism.…”

Section: Discussionmentioning

confidence: 56%

“…The etiology of autism is unclear but it is known that it arises in early childhood. The disease symptoms include impaired reciprocal social interactions, isolated interests, epilepsy, motor defects, gastrointestinal abnormalities, aggression, hyperactivity and sleep and mood disorders [1][2][3][4]. Among these, ste-reotypical behavior, impaired verbal or nonverbal communication and delayed social interaction are the main symptoms [5].…”

Section: Introductionmentioning

confidence: 99%

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New substitutions of mitochondrial DNA in Iranian autistic children

Akouchekian¹,

Shooshtari²,

Heidary³

et al. 2018

Arch Med Sci Civil Dis

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Introduction: Autism spectrum disorders (ASDs) are neurodevelopmentally complex diseases with causative de-novo and inherited genetic factors. They contain a range of cognitive and behavioral conditions such as Asperger's syndrome, pervasive developmental disorder and autism. Our study subjects were children with autistic behaviors (15-60 CARS Score). Material and methods: The DNA extraction process was done using a GeNet Bio DNA extraction kit, and the region of interest was amplified using independent PCR runs. After purification of PCR products, both strands were sequenced by the Big Dye Termination system. The automated sequencing on an ABI 3700 was directly determined with a capillary sequencer machine. Both primers' sequencing results were analyzed using a bioinformatics tool, Sequencher Software 5. Results: In the population we studied, the variant G9055A (located at ATP6) was reported to be pathogenic (CAAD > 20 and PolyPhen shows it to be probably damaging). In this variant amino acid alanine converts to threonine. A to T substitutions induce accumulation of amyloid fibril in the brain because threonine prefers to form a β sheet as a necessary stage in the amyloidogenic process. Conclusions: In our study of patients with autism, we found one case having an interesting association with amyloidosis. It is hoped that by finding such markers, the children will be treated with more certainty.

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“…MT-CO2 is a mitochondrion-encoded subunit of cytochrome c that is a critical component of the oxidative phosphorylation pathway. A mutation in the MT-CO2 gene (mitochondrion DNA 8033A > G (Ile → Val)) has been detected in autistic children (Avdjieva-Tzavella et al 2012). UQCRC1 is a subunit of mitochondrial respiratory complex III and determines complex III activity.…”

Section: Nlgn3 and Mitochondrial Functionmentioning

confidence: 98%

Novel Interactive Partners of Neuroligin 3: New Aspects for Pathogenesis of Autism

et al. 2014

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Autism is a neurodevelopmental disorder with a strong genetic predisposition. Neurolign 3 (NLGN3) as a postsynaptic transmembrane protein, functions in both neuron synaptogenesis and glia-neuron communications. Previously, a gain of function mutation (R451C) in NLGN3 was identified in autistic patients, which illustrates the involvement of NLGN3 in autism pathogenesis. As proper synaptic targeting and functioning are controlled by intracellular protein interactions, in the current study, we tried to discover the intracellular regulation network in which NLGN3 might be involved by a yeast two-hybrid-based interactor identification. Fifty-one protein candidate partners were identified after screening a human fetal complementary DNA (cDNA) library with an intracellular fragment of NLGN3. The interactions of NLGN3 with a subset of candidates, including EEF1A1, FLNA, ITPRIP, CYP11A1, MT-CO2, GPR175, ACOT2, and QPRT, were further validated in human neuroblastoma cells or brain tissues. Furthermore, our study suggested that NLGN3 was functioning in cytosolic calcium balance and participating in calcium-regulated cellular processes. Our findings of novel NLGN3 binding partners provide evidences of involvement of NLGN3 in multiple biological pathways, especially calcium regulating and mitochondrial function, thus suggesting further significance. This new data not only leads to a better understanding of the physiological functions of NLGN3, but also provide new aspects for pathogenesis of autism.

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Mitochondrial DNA Mutations in two Bulgarian Children with Autistic Spectrum Disorders

Cited by 15 publications

References 25 publications

Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder

Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder

New substitutions of mitochondrial DNA in Iranian autistic children

Novel Interactive Partners of Neuroligin 3: New Aspects for Pathogenesis of Autism

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