fa شناسایی یک واریانت بی‌معنی جدید در ژن ABCD1 در یک بیمار مبتلا به آدرنولکودیستروفی از طریق توالی یابی کل اگزوم علوم پایه Basic Sciences پژوهشي اصیل Original Atricle <span style="font-size:11pt"><span style="line-height:101%"><span style="direction:rtl"><span style="unicode-bidi:embed"><span calibri="" style="font-family:"><b><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:101%"><span b="" nazanin="" style="font-family:"><span style="color:black">مقدمه:</span></span></span></span></b><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:101%"><span b="" nazanin="" style="font-family:"><span style="color:black"> آدرنولکودیستروفی، یک اختلال نورودژنراتیو پیشرونده است که معمولاً به صورت وابسته به کروموزوم</span></span></span></span><span dir="LTR" style="font-size:9.0pt"><span style="line-height:101%"><span new="" roman="" style="font-family:" times=""><span style="color:black"> X </span></span></span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:101%"><span b="" nazanin="" style="font-family:"><span style="color:black">به ارث می‌رسد. این بیماری شایع‌ترین اختلال پراکسیزومی است و در نتیجه‌ جهش در ژن </span></span></span></span><i><span dir="LTR" style="font-size:9.0pt"><span style="line-height:101%"><span new="" roman="" style="font-family:" times=""><span style="color:black">ABCD1</span></span></span></span></i><b><i> </i></b><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:101%"><span b="" nazanin="" style="font-family:"><span style="color:black">ایجاد می‌شود. تظاهرات بیماری بر اساس سن شروع ابتلا، بسیار متفاوت است. بروز تقریبی آن حدود </span></span></span></span><span lang="FA" style="font-size:9.0pt"><span style="line-height:101%"><span b="" nazanin="" style="font-family:"><span style="color:black">۱</span></span></span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:101%"><span b="" nazanin="" style="font-family:"><span style="color:black"> در هر </span></span></span></span><span lang="FA" style="font-size:9.0pt"><span style="line-height:101%"><span b="" nazanin="" style="font-family:"><span style="color:black">۱۷000</span></span></span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:101%"><span b="" nazanin="" style="font-family:"><span style="color:black"> تولد زنده تخمین زده شده است. هدف از این مطالعه، بررسی ژنتیکی یک فرد مبتلا به آدرنولکودیستروفی وابسته به</span></span></span></span> <span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:101%"><span b="" nazanin="" style="font-family:"><span style="color:black">کروموزوم </span></span></span></span><span dir="LTR" style="font-size:9.0pt"><span style="line-height:101%"><span new="" roman="" style="font-family:" times=""><span style="color:black">&nbsp;X</span></span></span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:101%"><span b="" nazanin="" style="font-family:"><span style="color:black">بود. </span></span></span></span><span lang="FA" style="line-height:101%"><span b="" nazanin="" style="font-family:"><span style="color:black"></span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:104%"><span style="direction:rtl"><span style="unicode-bidi:embed"><span calibri="" style="font-family:"><b><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:104%"><span b="" nazanin="" style="font-family:"><span style="color:black">روش کار:</span></span></span></span></b><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:104%"><span b="" nazanin="" style="font-family:"><span style="color:black"> نمونه‌ خون محیطی از بیماری با علائم بالینی منطبق با آدرنولکودیستروفی جمع‌آوری شد.</span></span></span></span><span dir="LTR" style="font-size:9.0pt"><span style="line-height:104%"><span new="" roman="" style="font-family:" times=""><span style="color:black"> DNA </span></span></span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:104%"><span b="" nazanin="" style="font-family:"><span style="color:black">ژنومی استخراج و سپس توالی‌یابی کل اگزوم</span></span></span></span> <span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:104%"><span b="" nazanin="" style="font-family:"><span style="color:black">به منظور شناسایی واریانت‌های ژنتیکی احتمالی انجام شد. بعد از تحلیل داده‌ها، واریانت شناسایی شده جهت تأیید با روش سنگر مورد بررسی قرار گرفت. همچنین مادر فرد بیمار جهت وضعیت ناقل بودن مورد بررسی قرار گرفت. تمام اصول اخلاقی مطابق با دستورالعمل‌های کمیته ملی اخلاق در پژوهش‌های زیست‌پزشکی و استانداردهای </span></span></span></span><span dir="LTR" style="font-size:9.0pt"><span style="line-height:104%"><span new="" roman="" style="font-family:" times=""><span style="color:black">COPE</span></span></span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:104%"><span b="" nazanin="" style="font-family:"><span style="color:black"> رعایت شده‌اند.</span></span></span></span><span dir="LTR" style="font-size:10.0pt"><span style="line-height:104%"><span new="" roman="" style="font-family:" times=""><span style="color:black"></span></span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:102%"><span style="direction:rtl"><span style="unicode-bidi:embed"><span calibri="" style="font-family:"><b><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:102%"><span b="" nazanin="" style="font-family:"><span style="color:black">یافته‌ها:</span></span></span></span></b><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:102%"><span b="" nazanin="" style="font-family:"><span style="color:black"> در این مطالعه، یک واریانت بیماری‌زای همی‌زیگوت در ژن </span></span></span></span><i><span dir="LTR" style="font-size:9.0pt"><span style="line-height:102%"><span new="" roman="" style="font-family:" times=""><span style="color:black">ABCD1</span></span></span></span></i> &nbsp;<span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:102%"><span b="" nazanin="" style="font-family:"><span style="color:black">با مشخصات</span></span></span></span><span dir="LTR" style="font-size:9.0pt"><span style="line-height:102%"><span new="" roman="" style="font-family:" times=""><span style="color:black"> (NM_000033.4): c.1777G>T (p.Gly593Ter) </span></span></span></span><span lang="FA" style="font-size:9.0pt"><span style="line-height:102%"><span b="" nazanin="" style="font-family:"><span style="color:black">&nbsp;و به صورت بی‌معنی </span></span></span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:102%"><span b="" nazanin="" style="font-family:"><span style="color:black">در بیمار شناسایی شد و در نتیجه تشخیص آدرنولکودیستروفی وابسته به</span></span></span></span><span dir="LTR" style="font-size:9.0pt"><span style="line-height:102%"><span new="" roman="" style="font-family:" times=""><span style="color:black">&nbsp; X-ALD) X </span></span></span></span><span lang="AR-SA" style="font-size:9.0pt"><span style="line-height:102%"><span b="" nazanin="" style="font-family:"><span style="color:black">در وی تأیید گردید. همچنین مادر جهت واریانت شناسایی شده ناقل است</span></span></span></span><span lang="FA" style="font-size:9.0pt"><span style="line-height:102%"><span b="" nazanin="" style="font-family:"><span style="color:black">.</span></span></span></span> <span dir="LTR" style="font-size:10.0pt"><span style="line-height:102%"><span new="" roman="" style="font-family:" times=""><span style="color:black"></span></span></span></span></span></span></span></span></span><br> <b><span dir="RTL" lang="AR-SA" style="font-size:9.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.1pt">نتیجه‌گیری:</span></span></span></span></span></b><span dir="RTL" lang="AR-SA" style="font-size:9.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.1pt"> جهش همی‌زیگوت در ژن</span></span></span></span></span> <i><span style="font-size:9.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times=""><span style="color:black"><span style="letter-spacing:-.1pt">ABCD1</span></span></span></span></span></i> <span dir="RTL" lang="AR-SA" style="font-size:9.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.1pt">با استفاده از روش توالی‌یابی کل اگزوم شناسایی شد. جهش در این ژن منجر به بروز بیماری آدرنولکودیستروفی وابسته به</span></span></span></span></span><span style="font-size:9.0pt"><span style="line-height:115%"><span new="" roman="" style="font-family:" times=""><span style="color:black"><span style="letter-spacing:-.1pt"> X </span></span></span></span></span><span dir="RTL" lang="AR-SA" style="font-size:9.0pt"><span style="line-height:115%"><span b="" nazanin="" style="font-family:"><span style="color:black"><span style="letter-spacing:-.1pt">می‌شود.</span></span></span></span></span> <span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span calibri="" style="font-family:"><b><span style="font-size:8.0pt"><span ms="" style="font-family:" trebuchet="">Introduction:</span></span></b><span style="font-size:8.0pt"><span ms="" style="font-family:" trebuchet=""> Adrenoleukodystrophy, inherited in an X-linked manner, is a progressive neurodegenerative disorder. It is the most common peroxisomal disorder and results from mutations in the ABCD1 gene. The disease manifests with a wide range of symptoms that can vary depending on the age of onset. Its estimated prevalence is approximately 1 in 17,000 live births. This study aimed to analyze the genetic profile of an individual with X-linked Adrenoleukodystrophy (X-ALD) through whole-exome sequencing.</span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span calibri="" style="font-family:"><b><span style="font-size:8.0pt"><span ms="" style="font-family:" trebuchet="">Methods:</span></span></b> <span lang="EN-GB" style="font-size:8.0pt"><span ms="" style="font-family:" trebuchet="">A peripheral blood sample was obtained from a patient with clinical features consistent with adrenoleukodystrophy. Following the extraction of genomic DNA, whole-exome sequencing (WES) was conducted to identify potential genetic variants. Subsequent data analysis revealed a disease-causing mutation, which was confirmed by Sanger sequencing. The patient&#39;s mother was also tested to determine her carrier status. All ethical considerations were observed in accordance with the guidelines established by the National Committee for Ethics in Biomedical Research and the COPE standards</span></span><span style="font-size:8.0pt"><span ms="" style="font-family:" trebuchet="">.</span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span calibri="" style="font-family:"><b><span style="font-size:8.0pt"><span ms="" style="font-family:" trebuchet="">Results: </span></span></b><span lang="EN-GB" style="font-size:8.0pt"><span ms="" style="font-family:" trebuchet="">The study identified a hemizygous variant in the ABCD1 gene, (NM_000033.4) c.1777G>T (p.Gly593Ter), likely pathogenic, confirming the patient&#39;s diagnosis of X-linked Adrenoleukodystrophy (X-ALD). Genetic analysis of the patient&rsquo;s mother revealed that she was a carrier</span></span><span style="font-size:8.0pt"><span ms="" style="font-family:" trebuchet="">.</span></span></span></span></span></span></span><br> <b><span style="font-size:8.0pt"><span style="line-height:115%"><span ms="" style="font-family:" trebuchet=""><span style="letter-spacing:-.2pt">Conclusions:</span></span></span></span></b> <span lang="EN-GB" style="font-size:8.0pt"><span style="line-height:115%"><span ms="" style="font-family:" trebuchet=""><span style="letter-spacing:-.2pt">A hemizygous variant in the ABCD1 gene was identified using whole exome sequencing. This variant can lead to X-linked Adrenoleukodystrophy</span></span></span></span><span style="font-size:8.0pt"><span style="line-height:115%"><span ms="" style="font-family:" trebuchet=""><span style="letter-spacing:-.2pt">.</span></span></span></span> آدرنولکودیستروفی؛ ژن ABCD1؛ جهش؛ توالی‌یابی کل اگزوم Adrenoleukodystrophy, ABCD1, Mutation, Whole-exome sequencing 459 465 http://jams.arakmu.ac.ir/browse.php?a_code=A-10-7239-5&slc_lang=fa&sid=1 Reyhaneh Khodadadi ریحانه خدادادی khodadadi.r96@gmail.com 4600319475328460092198 0009-0003-6834-2963 No Department of Biology, Faculty of Science, Arak University, Arak, Iran گروه زیست‌شناسی، دانشکده علوم، دانشگاه اراک، اراک، ایران Sahar Bayat سحر بیات Bayatsahar40@gmail.com 4600319475328460092199 4600319475328460092199 No Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Iran گروه بیوشیمی و ژنتیک، دانشکده پزشکی، دانشگاه علوم پزشکی اراک، اراک، ایران Samaneh Sadati سمانه ساداتی sadati4007@yahoo.com 4600319475328460092200 0009-0002-8505-0279 No Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran گروه ژنتیک، مرکز تحقیقات پزشکی تولیدمثل، پژوهشگاه تولید مثل رویان، تهران، ایران Milad Gholami میلاد غلامی mtu.q220@gmail.com 4600319475328460092201 4600319475328460092201 Yes Department of Biochemistry and Genetics, School of Medicine, Arak University of Medical Sciences, Arak, Iran گروه ژنتیک، مرکز تحقیقات پزشکی تولیدمثل، پژوهشگاه تولید مثل رویان، تهران، ایران