<p>Sir,</p> <p>Autism spectrum disorders (ASD) are the most heritable complex disorders. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>Although there have been many efforts to locate the genes associated with ASD risk, the genetics of ASD has not been elucidated. <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref5">5</xref> </sup>Some studies have confirmed the contribution of mitochondrial genome mutations to the pathophysiology of autism, <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>but other studies have rejected such a contribution. <sup> <xref ref-type="bibr" rid="ref7">7</xref> </sup>In the current study (research project number #17), we have investigated the association between mitochondrial tRNA gene mutations and the risk of autism.</p> <p>Deoxyribonucleic acid (DNA) was extracted from the blood of 24 ASD patients in the Special Medical Center of Tehran, Iran, during 2010-2011, and 40 age-matched, healthy controls (QIAamp DNA Micro kit, Germany). Twenty-two tRNA genes of the mitochondrial genome were polymerase chain reaction (PCR)-amplified, using 12 primer pairs, and then sequenced. The sequencing results were screened for mutations using the clustalW Program and the association of the mutations with autism risk was assessed by statistical analysis, using the SPSS version 15.</p> <p>Many of the observed mutations were sporadic mutations without any significant relationship with the risk of autism, while other mutations, including those of high frequency, showed no significant relationship with the risk of disease (P-value > 0.05), except mutations 16126T>C (P-value = 0.01), 14569G>A (P-value = 0.02), and 1811A>G (P-value = 0.04). These three mutations were in the non-coding regions of the mitochondrial genome, near the tRNA genes. The mutation 16126T>C was in the mtDNA control region.</p> <p>Our study showed a significant relationship between the point mutations 16126T>C, 14569G>A, and 1811A>G of the mitochondrial genome and the risk of autism.</p> </sec> </body> <back> <ref-list> <ref id="ref1"> <label>1</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Bayou</surname> <given-names>N</given-names> </name> <name> <surname>M′Rad</surname> <given-names>R</given-names> </name> <name> <surname>Ahlem</surname> <given-names>B</given-names> </name> <name> <surname>Bechir Helayem</surname> <given-names>M</given-names> </name> <name> <surname>Chaabouni</surname> <given-names>H</given-names> </name> </person-group> <article-title>Autism: An overview of genetic aetiology</article-title> <source>Tunis Med</source> <year>2008</year> <volume>86</volume> <fpage>573</fpage> <lpage>8</lpage> </nlm-citation> </ref> <ref id="ref2"> <label>2</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Muhle</surname> <given-names>R</given-names> </name> <name> <surname>Trentacoste</surname> <given-names>SV</given-names> </name> <name> <surname>Rapin</surname> <given-names>I</given-names> </name> </person-group> <article-title>The genetics of autism</article-title> <source>Pediatrics</source> <year>2004</year> <volume>113</volume> <fpage>e472</fpage> <lpage>86</lpage> </nlm-citation> </ref> <ref id="ref3"> <label>3</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Rossignol</surname> <given-names>DA</given-names> </name> <name> <surname>Frye</surname> <given-names>RE</given-names> </name> </person-group> <article-title>Mitochondrial dysfunction in autism spectrum disorders: A systematic review and meta-analysis</article-title> <source>Mol Psychiatry</source> <year>2011</year> <volume>17</volume> <fpage>290</fpage> <lpage>314</lpage> </nlm-citation> </ref> <ref id="ref4"> <label>4</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Weissman</surname> <given-names>JR</given-names> </name> <name> <surname>Kelley</surname> <given-names>RI</given-names> </name> <name> <surname>Bauman</surname> <given-names>ML</given-names> </name> <name> <surname>Cohen</surname> <given-names>BH</given-names> </name> <name> <surname>Murray</surname> <given-names>KF</given-names> </name> <name> <surname>Mitchell</surname> <given-names>RL</given-names> </name> <etal /> </person-group> <article-title>Mitochondrial disease in autism spectrum disorder patients: A cohort analysis</article-title> <source>PLoS One</source> <year>2008</year> <volume>3</volume> <fpage>e3815</fpage> <lpage>20</lpage> </nlm-citation> </ref> <ref id="ref5"> <label>5</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Zhang</surname> <given-names>B</given-names> </name> <name> <surname>Angelidou</surname> <given-names>A</given-names> </name> <name> <surname>Alysandratos</surname> <given-names>KD</given-names> </name> <name> <surname>Vasiadi</surname> <given-names>M</given-names> </name> <name> <surname>Francis</surname> <given-names>K</given-names> </name> <name> <surname>Asadi</surname> <given-names>S</given-names> </name> <etal /> </person-group> <article-title>Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic children</article-title> <source>J Neuroinflammation</source> <year>2010</year> <volume>7</volume> <fpage>80</fpage> <lpage>4</lpage> </nlm-citation> </ref> <ref id="ref6"> <label>6</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Virgilio</surname> <given-names>R</given-names> </name> <name> <surname>Ronchi</surname> <given-names>D</given-names> </name> <name> <surname>Bordoni</surname> <given-names>A</given-names> </name> <name> <surname>Fassone</surname> <given-names>E</given-names> </name> <name> <surname>Bonato</surname> <given-names>S</given-names> </name> <name> <surname>Donadoni</surname> <given-names>C</given-names> </name> <etal /> </person-group> <article-title>Mitochondrial DNA G8363A mutation in the tRNA Lys gene: Clinical, biochemical and pathological study</article-title> <source>J Neurol Sci</source> <year>2009</year> <volume>281</volume> <fpage>85</fpage> <lpage>92</lpage> </nlm-citation> </ref> <ref id="ref7"> <label>7</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Alvarez-Iglesias</surname> <given-names>V</given-names> </name> <name> <surname>Mosquera-Miguel</surname> <given-names>A</given-names> </name> <name> <surname>Cusco</surname> <given-names>I</given-names> </name> <name> <surname>Carracedo</surname> <given-names>A</given-names> </name> <name> <surname>Perez-Jurado</surname> <given-names>LA</given-names> </name> <name> <surname>Salas</surname> <given-names>A</given-names> </name> </person-group> <article-title>Reassessing the role of mitochondrial DNA mutations in autism spectrum disorder</article-title> <source>BMC Med Genet</source> <year>2011</year> <volume>12</volume> <fpage>50</fpage> <lpage>6</lpage> </nlm-citation> </ref> <ref id="ref8"> <label>8</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"></person-group> <article-title></article-title> <source></source> <year></year> <volume></volume> <fpage></fpage> </nlm-citation> </ref> </ref-list> </back> </article>

JRMS

J Res Med Sci

Journal of Research in Medical Sciences

1735-1995 1735-7136

Medknow Publications Pvt Ltd

India

JRMS-18-926

24497871

Letter to Editor

Association of human mtDNA mutations with autism in Iranian patients

Mousavizadeh

Kazem

Askari

Mohammad

Arian

Hajar

Gourjipour

Fazel

Nikpour

Amin R

Tavafjadid

Maryam

Aryani

Omid

Kamalidehghan

Behnam

Maroof

Hamid R

Houshmand

Massoud

Department of Molecular Biology, Cellular and Molecular Research Center, Tehran, Iran Department of Biotechnology, College of Allied Medicine, Tehran, Iran Department of Medical Genetic, Special Medical Center, Tehran, Iran Department of Molecular Biology, HIV Molecular Research Laboratory, School of Public Health and Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran Department of Immunology, Kerman University of Medical Sciences, Kerman, Iran Department of Molecular Biology, Cellular and Molecular Research Center, Tehran, Iran Department of Medical Genetic, Special Medical Center, Tehran, Iran Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Department of Medical Genetic, Special Medical Center, Tehran, Iran Department of Medical Genetic, Special Medical Center; Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran

Address for correspondence:Massoud Houshmand, Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran massoudh@nigeb.ac.ir

October 2013

18 10 926 926

2013

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

<p>Sir,</p> <p>Autism spectrum disorders (ASD) are the most heritable complex disorders. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>Although there have been many efforts to locate the genes associated with ASD risk, the genetics of ASD has not been elucidated. <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref5">5</xref> </sup>Some studies have confirmed the contribution of mitochondrial genome mutations to the pathophysiology of autism, <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>, <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>but other studies have rejected such a contribution. <sup> <xref ref-type="bibr" rid="ref7">7</xref> </sup>In the current study (research project number #17), we have investigated the association between mitochondrial tRNA gene mutations and the risk of autism.</p> <p>Deoxyribonucleic acid (DNA) was extracted from the blood of 24 ASD patients in the Special Medical Center of Tehran, Iran, during 2010-2011, and 40 age-matched, healthy controls (QIAamp DNA Micro kit, Germany). Twenty-two tRNA genes of the mitochondrial genome were polymerase chain reaction (PCR)-amplified, using 12 primer pairs, and then sequenced. The sequencing results were screened for mutations using the clustalW Program and the association of the mutations with autism risk was assessed by statistical analysis, using the SPSS version 15.</p> <p>Many of the observed mutations were sporadic mutations without any significant relationship with the risk of autism, while other mutations, including those of high frequency, showed no significant relationship with the risk of disease (P-value > 0.05), except mutations 16126T>C (P-value = 0.01), 14569G>A (P-value = 0.02), and 1811A>G (P-value = 0.04). These three mutations were in the non-coding regions of the mitochondrial genome, near the tRNA genes. The mutation 16126T>C was in the mtDNA control region.</p> <p>Our study showed a significant relationship between the point mutations 16126T>C, 14569G>A, and 1811A>G of the mitochondrial genome and the risk of autism.</p> </sec> </body> <back> <ref-list> <ref id="ref1"> <label>1</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Bayou</surname> <given-names>N</given-names> </name> <name> <surname>M′Rad</surname> <given-names>R</given-names> </name> <name> <surname>Ahlem</surname> <given-names>B</given-names> </name> <name> <surname>Bechir Helayem</surname> <given-names>M</given-names> </name> <name> <surname>Chaabouni</surname> <given-names>H</given-names> </name> </person-group> <article-title>Autism: An overview of genetic aetiology</article-title> <source>Tunis Med</source> <year>2008</year> <volume>86</volume> <fpage>573</fpage> <lpage>8</lpage> </nlm-citation> </ref> <ref id="ref2"> <label>2</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Muhle</surname> <given-names>R</given-names> </name> <name> <surname>Trentacoste</surname> <given-names>SV</given-names> </name> <name> <surname>Rapin</surname> <given-names>I</given-names> </name> </person-group> <article-title>The genetics of autism</article-title> <source>Pediatrics</source> <year>2004</year> <volume>113</volume> <fpage>e472</fpage> <lpage>86</lpage> </nlm-citation> </ref> <ref id="ref3"> <label>3</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Rossignol</surname> <given-names>DA</given-names> </name> <name> <surname>Frye</surname> <given-names>RE</given-names> </name> </person-group> <article-title>Mitochondrial dysfunction in autism spectrum disorders: A systematic review and meta-analysis</article-title> <source>Mol Psychiatry</source> <year>2011</year> <volume>17</volume> <fpage>290</fpage> <lpage>314</lpage> </nlm-citation> </ref> <ref id="ref4"> <label>4</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Weissman</surname> <given-names>JR</given-names> </name> <name> <surname>Kelley</surname> <given-names>RI</given-names> </name> <name> <surname>Bauman</surname> <given-names>ML</given-names> </name> <name> <surname>Cohen</surname> <given-names>BH</given-names> </name> <name> <surname>Murray</surname> <given-names>KF</given-names> </name> <name> <surname>Mitchell</surname> <given-names>RL</given-names> </name> <etal /> </person-group> <article-title>Mitochondrial disease in autism spectrum disorder patients: A cohort analysis</article-title> <source>PLoS One</source> <year>2008</year> <volume>3</volume> <fpage>e3815</fpage> <lpage>20</lpage> </nlm-citation> </ref> <ref id="ref5"> <label>5</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Zhang</surname> <given-names>B</given-names> </name> <name> <surname>Angelidou</surname> <given-names>A</given-names> </name> <name> <surname>Alysandratos</surname> <given-names>KD</given-names> </name> <name> <surname>Vasiadi</surname> <given-names>M</given-names> </name> <name> <surname>Francis</surname> <given-names>K</given-names> </name> <name> <surname>Asadi</surname> <given-names>S</given-names> </name> <etal /> </person-group> <article-title>Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic children</article-title> <source>J Neuroinflammation</source> <year>2010</year> <volume>7</volume> <fpage>80</fpage> <lpage>4</lpage> </nlm-citation> </ref> <ref id="ref6"> <label>6</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Virgilio</surname> <given-names>R</given-names> </name> <name> <surname>Ronchi</surname> <given-names>D</given-names> </name> <name> <surname>Bordoni</surname> <given-names>A</given-names> </name> <name> <surname>Fassone</surname> <given-names>E</given-names> </name> <name> <surname>Bonato</surname> <given-names>S</given-names> </name> <name> <surname>Donadoni</surname> <given-names>C</given-names> </name> <etal /> </person-group> <article-title>Mitochondrial DNA G8363A mutation in the tRNA Lys gene: Clinical, biochemical and pathological study</article-title> <source>J Neurol Sci</source> <year>2009</year> <volume>281</volume> <fpage>85</fpage> <lpage>92</lpage> </nlm-citation> </ref> <ref id="ref7"> <label>7</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Alvarez-Iglesias</surname> <given-names>V</given-names> </name> <name> <surname>Mosquera-Miguel</surname> <given-names>A</given-names> </name> <name> <surname>Cusco</surname> <given-names>I</given-names> </name> <name> <surname>Carracedo</surname> <given-names>A</given-names> </name> <name> <surname>Perez-Jurado</surname> <given-names>LA</given-names> </name> <name> <surname>Salas</surname> <given-names>A</given-names> </name> </person-group> <article-title>Reassessing the role of mitochondrial DNA mutations in autism spectrum disorder</article-title> <source>BMC Med Genet</source> <year>2011</year> <volume>12</volume> <fpage>50</fpage> <lpage>6</lpage> </nlm-citation> </ref> <ref id="ref8"> <label>8</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"></person-group> <article-title></article-title> <source></source> <year></year> <volume></volume> <fpage></fpage> </nlm-citation> </ref> </ref-list> </back> </article>