en شناسایی جهش‌های tRNA سیستئین و تیروزین میتوکندریایی در زنان ایرانی مبتلا به سقط مکرر ایدیوپاتیک: یک مطالعه مورد-شاهدی Reproductive Genetics Original Article Original Article <div style="text-align: justify;"><span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span sans-serif="" style="font-family:Calibri,"><b><span b="" lang="FA" mitra="" style="font-family:">مقدمه: </span></b><span b="" lang="FA" mitra="" style="font-family:">سقط مکرر جنین یکی از شایع‌ترین بیماری‌های تولید&shy;مثلی است. چندین عامل از جمله اختلالات ژنتیکی والدین، اختلالات هورمونی و اختلالات ایمنی مادر خطر ابتلای به سقط مکرر را افزایش می‌دهند. نیمی از موارد سقط مکرر هم بدون علت شناخته‌ شده هستند. برخی از جهش‌های ژنوم میتوکندری (</span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">mt-DNA</span></span><span b="" lang="FA" mitra="" style="font-family:">) به سقط مکرر منجر می‌شوند. نیمی از اختلالات میتوکندریایی به واسطه جهش در ژن‌های </span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">tRNA</span></span><span b="" mitra="" style="font-family:"> میتوکندری (</span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">mt-tRNA</span></span><span b="" lang="FA" mitra="" style="font-family:">) ایجاد می‌شوند.</span><span dir="LTR" style="font-family:"Arial","sans-serif""></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span sans-serif="" style="font-family:Calibri,"><b><span b="" lang="FA" mitra="" style="font-family:">هدف: </span></b><span b="" lang="FA" mitra="" style="font-family:">این مطالعه به منظور شناسایی جهش‌های </span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">tRNA</span></span> <span b="" lang="FA" mitra="" style="font-family:">سیستئین و تیروزین میتوکندریایی در بیماران مبتلا به سقط مکرر ایدیوپاتیک می‌باشد.</span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span sans-serif="" style="font-family:Calibri,"><b><span b="" lang="FA" mitra="" style="font-family:">مواد و روش&shy; ها: </span></b><span b="" lang="FA" mitra="" style="font-family:">در این مطالعه مورد-شاهدی 100 زن مبتلا به سقط مکرر با علل ناشناخته و 100 نمونه شاهد بدون هرگونه سابقه سقط، با تکنیک&nbsp;&nbsp;</span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">PCR-SSCP</span></span><span b="" mitra="" style="font-family:"> و تعیین توالی مورد بررسی قرار گرفتند. آنالیزهای بیوانفورماتیک بوسیله</span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MITOMAP</span></span> <span b="" lang="FA" mitra="" style="font-family:">،</span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MEGA4</span></span> <span b="" lang="FA" mitra="" style="font-family:">،</span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">MAMIT-tRNA </span></span><span b="" mitra="" style="font-family:">&nbsp;و سایر نرم&shy;افزارها</span> <span b="" lang="FA" mitra="" style="font-family:">انجام شد.</span><span lang="AR-SA" style="font-size:14.0pt"><span style="font-family:"B Nazanin""></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span sans-serif="" style="font-family:Calibri,"><b><span b="" lang="FA" mitra="" style="font-family:">نتایج: </span></b><span b="" lang="FA" mitra="" style="font-family:">در این پژوهش 4 جهش در ژن‌های </span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">mt-tRNA</span></span><span b="" mitra="" style="font-family:"> شناسایی شد. 1 جهش در </span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">tRNA</span></span><span b="" mitra="" style="font-family:"> سیستئین (</span> <span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">C>T</span></span><span b="" lang="FA" mitra="" style="font-family:">5824) و 3 جهش هم در </span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">tRNA</span></span> <span b="" lang="FA" mitra="" style="font-family:">تیروزین&nbsp; (</span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">T</span></span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">></span></span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">C</span></span> <span b="" lang="FA" mitra="" style="font-family:">5836، </span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">C>T</span></span><span b="" lang="FA" mitra="" style="font-family:"> 5849 و </span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">T>A</span></span> <span b="" lang="FA" mitra="" style="font-family:">5868) مشاهده شد.</span><span lang="AR-SA" style="font-size:14.0pt"><span style="font-family:"B Nazanin""></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="direction:rtl"><span style="unicode-bidi:embed"><span sans-serif="" style="font-family:Calibri,"><b><span b="" lang="FA" mitra="" style="font-family:">نتیجه&shy; گیری:</span></b> <span b="" lang="FA" mitra="" style="font-family:">از بین 4 جهش شناسایی شده، یکی از آنها جدید بود و قبلا گزارش نشده بود. آنالیزهای بیوانفورماتیک نشان داد که این جهش‌ها می‌توانند بیماری&shy;زا باشند. این جهش‌ها در نواحی حفاظت شده </span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">tRNA</span></span><span b="" lang="FA" mitra="" style="font-family:">ها ایجاد شده و سبب تغییر حالت پایدار این مولکول‌ها می‌شود که می‌تواند باعث نقص در عملکرد میتوکندری شود. جهش‌های این ژن‌ها ممکن است بتواند به ارزیابی سقط مکرر کمک نماید. مطالعه بیشتر جهش‌های احتمالی همه 22 </span><span dir="LTR" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">mt-tRNA</span></span><span b="" mitra="" style="font-family:"> میتوکندریایی به منظور بررسی نقش احتمالی آنها در سقط مکرر توصیه می‌گردد.</span><span lang="AR-SA" style="font-size:14.0pt"><span style="font-family:"B Nazanin""></span></span></span></span></span></span></span></div> <div style="text-align: justify;"><span style="font-family:Times New Roman;"><span style="font-size:11pt"><span style="line-height:normal"><span new="" roman="" times=""><b><span style="font-size:12.0pt">Background:</span></b><span style="font-size:12.0pt"> Recurrent miscarriage is one of the most prevalent reproductive diseases. This phenomenon has several reasons, including maternal, hormonal, immunological, and parental genetic factors. <a name="_Hlk139292574">Idiopathic recurrent miscarriage </a>(IRM), with no distinctive etiology, involves about half of the recurrent miscarriage cases. Some mutations in mitochondrial DNA can lead to miscarriage. Mitochondrial tRNA (mt-tRNA) mutations cause nearly half of the mitochondrial disorders. </span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span new="" roman="" times=""><b><span style="font-size:12.0pt">Objective:</span></b><b> </b><span style="font-size:12.0pt">To identify <i>mt-</i> <i>tRNA^{Cys & Tyr}</i>gene mutations in Iranian women with IRM.</span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span new="" roman="" times=""><b><span style="font-size:12.0pt">Materials and Methods:</span></b><span style="font-size:12.0pt"> In this case-control study, 100 Iranian women with IRM and 100 women as control without any history of miscarriage were investigated by polymerase chain reaction-single strand conformation polymorphism technique followed by gene sequencing. Bioinformatics analysis were done using human mitochondrial genome database, molecular evolutionary genetics analysis, mammalian mitochondrial-tRNA, etc.</span><span style="font-size:12.0pt"></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span new="" roman="" times=""><b><span style="font-size:12.0pt">Results:</span></b><span style="font-size:12.0pt"> Results showed 4 mt-tRNA mutations including 1 cysteine mt-tRNA mutation (5824C>T) and 3 tyrosine mt-tRNA mutations (5868T>A, 5849C>T, and 5836T>C) in our cases. </span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span new="" roman="" times=""><b><span style="font-size:12.0pt">Conclusion:</span></b><span style="font-size:12.0pt"> Amongst the 4 mutations found, one was novel that is still not reported. Our bioinformatics analysis revealed that these mutations can be pathogenic. They occurred in tRNA-conserved regions and their secondary structure was changed, which can result in mitochondrial dysfunction. Mutations of these genes may help in the assessment of IRM. Further study of all 22 mt-tRNAs possible mutations is recommended to describe their etiologic role in IRM.</span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span new="" roman="" style="font-family:" times=""><span style="font-size:10.0pt"></span></span></span></span></div> سقط مکرر, DNA میتوکندری, SNP, هتروپلاسمی. Recurrent early pregnancy loss, mtDNA, SNPs, Heteroplasmy. 567 576 http://ijrm.ir/browse.php?a_code=A-10-518-2&slc_lang=en&sid=1 Elham Mojodi elham.mojodi68@gmail.com 0000-0002-0850-4276 No Department of Biology, Faculty of Science, Yazd University, Yazd, Iran. Alimohammad Mosadegh Mehrjardi ali.moh.mosadegh@gmail.com 0000-0002-9146-9570 No Department of Traditional Pharmacy, Faculty of Traditional Medicine, Tehran University of Medical Sciences, Tehran, Iran. Yasaman Naeimzadeh yasamannaeimzadeh@gmail.com 0000-0003-3937-1426 No Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran. Nasrin Ghasemi nghasemi479@gmail.com 0000-0002-1103-6004 No Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Ali Falahati ali.falahati@yazd.ac.ir 0000-0001-7384-9425 No Department of Biology, Faculty of Science, Yazd University, Yazd, Iran. Seyed Mohammad Moshtaghioun moshtaghiun@yazd.ac.ir 0000-0002-6281-9674 Yes Department of Biology, Faculty of Science, Yazd University, Yazd, Iran.