BASIC RESEARCH
New substitutions of mitochondrial DNA in Iranian autistic children
 
More details
Hide details
 
Submission date: 2018-04-22
 
 
Final revision date: 2018-06-24
 
 
Acceptance date: 2018-07-01
 
 
Publication date: 2018-10-08
 
 
Arch Med Sci Civil Dis 2018;3(1):87-91
 
KEYWORDS
TOPICS
ABSTRACT
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  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.

 
REFERENCES (30)
1.
Avdjieva-Tzavella D, Mihailova S, Lukanov C, et al. Mitochondrial DNA mutations in two Bulgarian children with autistic spectrum disorders. Balkan J Med Genet 2012; 15: 47-54.
 
2.
Patowary A, Nesbitt R, Archer M, Bernier R, Brkanac Z. Next generation sequencing mitochondrial DNA analysis in autism spectrum disorder. Autism Res 2017; 10: 1338-43.
 
3.
Penagarikano O. New therapeutic options for autism spectrum disorder: experimental evidences. Exp Neurobiol 2015; 24: 301-11.
 
4.
Tang G, Gutierrez Rios P, Kuo SH, et al. Mitochondrial abnormalities in temporal lobe of autistic brain. Neurobiol Dis 2013; 54: 349-61.
 
5.
Piryaei F, Houshmand M, Aryani O, Dadgar S, Soheili ZS. Investigation of the mitochondrial ATPase 6/8 and tRNA (Lys) genes mutations in autism. Cell J 2012; 14: 98-101.
 
6.
Craven L, Alston CL, Taylor RW, Turnbull DM. Recent advances in mitochondrial disease. Annu Rev Genomics Hum Genet 2017; 18: 257-75.
 
7.
Wei W, Keogh MJ, Wilson I, et al. Mitochondrial DNA point mutations and relative copy number in 1363 disease and control human brains. Acta Neuropathol Commun 2017; 5: 13.
 
8.
Gonder MK, Mortensen HM, Reed FA, de Sousa A, Tishkoff SA. Whole-mtDNA genome sequence analysis of ancient African lineages. Mol Biol Evol 2007; 24: 757-68.
 
9.
Samadi SA, McConkey R. Autism in developing countries: lessons from Iran. Autism Res Treatment 2011; 2011: 145359.
 
10.
Rosti RO, Sadek AA, Vaux KK, Gleeson JG. The genetic landscape of autism spectrum disorders. Develop Med Child Neurol 2014; 56: 12-8.
 
11.
Van Der Walt JM, Nicodemus KK, Martin ER, et al. Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Am J Human Genet 2003; 72: 804-11.
 
12.
Anitha A, Nakamura K, Thanseem I, et al. Brain region-specific altered expression and association of mitochondria-related genes in autism. Mol Autism 2012; 3: 12.
 
13.
Frye RE, Rose S, Slattery J, MacFabe DF. Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome. Microb Ecol Health Dis 2015; 26: 27458.
 
14.
Siddiqui MF, Elwell C, Johnson MH. Mitochondrial dysfunction in autism spectrum disorders. Autism Open Access 2016; 6: 1000190.
 
15.
Napoli E, Wong S, Hertz-Picciotto I, Giulivi C. Deficits in bioenergetics and impaired immune response in granulocytes from children with autism. Pediatrics 2014; 133: e1405-10.
 
16.
Houshmand M, Mousavizadeh K, Askari M, Nikpour AR, Mazidi M, Tavafjadid M. Association of mtDNA mutation with autism in Iranian patients. Int J Pediatr 2013; 1: 39-43.
 
17.
Podoly E, Hanin G, Soreq H. Alanine-to-threonine substitutions and amyloid diseases: butyrylcholinesterase as a case study. Chem Biol Interact 2010; 187: 64-71.
 
18.
Frackowiak J, Mazur-Kolecka B, Schanen NC, Brown WT, Wegiel J. The link between intraneuronal N-truncated amyloid-beta peptide and oxidatively modified lipids in idiopathic autism and dup (15q11. 2-q13)/autism. Acta Neuropathol Commun 2013; 1: 61.
 
19.
Ray B, Long JM, Sokol DK, Lahiri DK. Increased secreted amyloid precursor protein-alpha (sAPPalpha) in severe autism: proposal of a specific, anabolic pathway and putative biomarker. PLoS One 2011; 6: e20405.
 
20.
Podoly E, Hanin G, Soreq H. Alanine-to-threonine substitutions and amyloid diseases: butyrylcholinesterase as a case study. Chem Biol Interact 2010; 187: 64Y71.
 
21.
Spillantini MG, Goedert M, Jakes R, Klug A. alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with lewy bodies. Proc Natl Acad Sci USA 1990; 87: 3947-51.
 
22.
Chou PY, Fasman GD. Conformational parameters for amino acids in helical, beta sheet, and random coil regions calculated from proteins. Biochemistry 1974; 13: 211-22.
 
23.
Sanders KM. Amyloid precursor protein processing in autism and Alzheimer’s disease and the potential therapeutic use of trehalose. ND dissertation, College of Naturopathic Medicine, Univ. of Bridgeport, Bridgeport, CT, 2013.
 
24.
Sokol DK, Chen D, Farlow MR, et al. High levels of Alzheimer beta-amyloid precursor protein (APP) in children with severely autistic behavior and aggression. J Child Neurol 2006; 21: 444-9.
 
25.
Crespi B. Autism and cancer risk. Autism Res 2011; 4: 302-10.
 
26.
Ingudomnukul E, Baron-Cohen S, Wheelwright S, Knickmeyer R. Elevated rates of testosterone-related disorders in women with autism spectrum conditions. Horm Behav 2007; 51: 597-604.
 
27.
Crawley JN, Heyer WD, LaSalle JM. Autism and cancer share risk genes, pathways, and drug targets. Trends Genet 2016; 32: 139-46.
 
28.
Liou GY, Storz P. Reactive oxygen species in cancer. Free Rad Res 2010; 44: 479-96.
 
29.
Ghaffarpour M, Mahdian R, Fereidooni F, Kamalidehghan B, Moazami N, Houshmand M. The mitochondrial ATPase6 gene is more susceptible to mutation than the ATPase8 gene in breast cancer patients. Cancer Cell Int 2014; 14: 21.
 
30.
Frye RE, Rossignol DA. Mitochondrial dysfunction can connect the diverse medical symptoms associated with autism spectrum disorders. Pediatr Res 2011; 69: 41R-7R.
 
ISSN:2451-0637
Journals System - logo
Scroll to top