fa بررسی فراوانی جهش cluster E6 در ژن CYP21A2 در بیماران مبتلا به هایپرپلازی مادرزادی آدرنال در جمعیت ایرانی پژوهشی Original <p dir="RTL" style="margin: 0px 0px 11px; text-align: justify; line-height: 150%; unicode-bidi: embed; direction: rtl;"><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: ">سابقه و هدف: هایپرپلازی مادرزادی آدرنال </span><span style="margin: 0px;" dir="LTR"></span><span style="margin: 0px;" dir="LTR"></span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times=""><span style="margin: 0px;" dir="LTR"></span><span style="margin: 0px;" dir="LTR"></span>(Congenital Adrenal Hyperplasia :CAH )</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span b="" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> <span lang="FA" style="margin: 0px;">نوعی بیماری ارثی با توارث اتوزم مغلوب است که در اغلب موارد بر اثر جهش در ژن </span></span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">CYP21A2 </span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;">&nbsp;</span>ایجاد میشود. هدف از این مطالعه بررسی فراوانی جهش </span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">cluster exon 6</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> در بین بیماران مبتلا به </span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">CAH</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> دارای نقص در آنزیم </span><span style="margin: 0px;" dir="LTR"></span><span style="margin: 0px;" dir="LTR"></span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times=""><span style="margin: 0px;" dir="LTR"></span><span style="margin: 0px;" dir="LTR"></span>21-OHD</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><i><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> در جمعیت ایرانی</span><span style="margin: 0px;" dir="LTR"></span><span style="margin: 0px;" dir="LTR"></span><span dir="LTR" lang="FA" new="" style="margin: 0px; line-height: 150%; font-family: " times=""><span style="margin: 0px;" dir="LTR"></span><span style="margin: 0px;" dir="LTR"></span> </span><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: ">می باشد.</span></i></p> <p dir="RTL" style="margin: 0px 0px 11px; text-align: justify; line-height: 150%; unicode-bidi: embed; direction: rtl;"><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: ">مواد و روش ها : <span style="margin: 0px;">تحقیق به روش توصیفی انجام گرفت</span><span style="margin: 0px;"> </span>و از تعداد 25 بیمار مبتلا به </span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">CAH</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><i><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> مراجعه کننده به بیمارستان علی اصغر تهران نمونه خون محیطی گرفته شد.<span style="margin: 0px;">&nbsp; </span>پس از استخراج </span><span style="margin: 0px;" dir="LTR"></span><span style="margin: 0px;" dir="LTR"></span><span dir="LTR" lang="FA" new="" style="margin: 0px; line-height: 150%; font-family: " times=""><span style="margin: 0px;" dir="LTR"></span><span style="margin: 0px;" dir="LTR"></span><span style="margin: 0px;">&nbsp;</span></span></i><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">DNA</span><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: ">ژنومی، ناحیه حاوی محل رخداد ژن </span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">cluster exon 6</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span b="" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> <span lang="FA" style="margin: 0px;">با روش </span></span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">PCR</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> تکثیر و سپس توالی یابی شدند</span><span style="margin: 0px;" dir="LTR"></span><span style="margin: 0px;" dir="LTR"></span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times=""><span style="margin: 0px;" dir="LTR"></span><span style="margin: 0px;" dir="LTR"></span>.</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> در نهایت با آنالیز توالی ها فراوانی حضور جهش </span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">cluster exon 6</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span b="" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> <span lang="FA" style="margin: 0px;">در جمعیت مورد مطالعه مشخص گردید.</span></span><span style='margin: 0px; line-height: 150%; font-family: "Times New Roman",serif; font-size: 12pt;' dir="LTR"></span></p> <p dir="RTL" style="margin: 0px 0px 11px; text-align: justify; line-height: 150%; unicode-bidi: embed; direction: rtl;"><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: ">یافته ها : <span style="margin: 0px;">&nbsp;15 بیمار(60%)</span><span style="margin: 0px;"> </span>دارای جهش </span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">cluster exon 6</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span b="" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> <span lang="FA" style="margin: 0px;">می باشد به طوری که در همه آنها سه جهش</span></span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">V236E , <span style="margin: 0px;">&nbsp;</span>I236N<span style="margin: 0px;">&nbsp; </span></span><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: ">و </span><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">M238K</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> به صورت هتروزیگوت مشاهده گردید. این جهش در والدین سالم این بیماران نیز به صورت هتروزیگوت شناسایی گردید.</span></p> <p dir="RTL" style="margin: 0px 0px 11px; text-align: justify; line-height: 150%; unicode-bidi: embed; direction: rtl;"><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: ">نتیجه گیری: <span style="margin: 0px;">به نظر می رسد</span><span style="margin: 0px;"> </span>که<font color="#000000"> جهش </font></span><font color="#000000"><span dir="LTR" new="" style="margin: 0px; line-height: 150%; font-family: " times="">cluster E6</span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span b="" lang="FA" style="margin: 0px; line-height: 150%; font-family: "><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> در فرم هتروزیگوت به تنهایی منجر به بیماری نمی شود و حتما باید وجود جهش های دیگر در ژن را بررسی کرد. کمااینکه احتمال دارد این جهش به صورت هتروزیگوت مرکب به همراه دیگر جهش های موجود در بقیه اگزون ها در بیماران تظاهر پیدا کند. </span></font></p> &nbsp; <p style="margin: 0px 0px 11px; text-align: justify; line-height: 150%;"><span lang="EN" new="" style="margin: 0px; color: rgb(34, 34, 34); font-family: " times=""><font size="3">Background: Congenital Adrenal Hyperplasia (CAH) is an inherited hereditary autosomal recessive heredity, which is often induced by mutation in the CYP21A2 gene. The aim of this study was to determine the prevalence of cluster exon 6 mutation among patients with CAH deficient in 21-OHD enzyme in Iranian population.</font></span></p> <p style="margin: 0px 0px 11px; text-align: justify; line-height: 150%;"><font size="3"><span lang="EN" new="" style="margin: 0px; color: rgb(34, 34, 34); font-family: " times="">Materials and Method</span><span lang="EN" new="" style="margin: 0px; font-family: " times="">s: </span><span new="" style="margin: 0px; font-family: " times="">This&nbsp;is a&nbsp;descriptive </span><span style="margin: 0px;"><font face="Calibri">study</font></span><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span><span dir="RTL" new="" style="margin: 0px; font-family: " times=""><span style="margin: 0px;" dir="RTL"></span><span style="margin: 0px;" dir="RTL"></span> </span><span new="" style="margin: 0px; font-family: " times="">and </span><span lang="EN" new="" style="margin: 0px; font-family: " times="">Blood samples were collected from 25 patients with CAH who referred to Ali Asghar Hospital in Tehran. After extraction of genomic DNA, the region containing the cluster gene exon 6 gene was amplified by PCR and then sequenced. Finally, by analyzing sequences, the frequency of cluster mutation exon 6 was determined in the population studied.</span></font></p> <p style="margin: 0px 0px 11px; text-align: justify; line-height: 150%;"><i><font size="3"><span lang="EN" new="" style="margin: 0px; font-family: " times="">Results: 15 patients (60%)<span lang="EN" new="" style="margin: 0px; font-family: " times=""> </span>had<span style="margin: 0px;"> an cluster mutation of exon 6, so that in all of them, three mutations V236E, I236N and M238K were observed as heterozygote. This mutation in the healthy parents of these patients were also identified as heterozygote.</span></span></font></i></p> <p style="margin: 0px 0px 11px; text-align: justify; line-height: 150%;"><font size="3"><i><span lang="EN" new="" style="margin: 0px; font-family: " times="">Conclusion:</span><span lang="EN" new="" style="margin: 0px; font-family: " times=""> </span></i><span new="" style="margin: 0px; font-family: " times="">it seems</span><i><span lang="EN" new="" style="margin: 0px; font-family: " times=""> that<span lang="EN" new="" style="margin: 0px; font-family: " times=""> </span>cluster E6 mutation in the heterozygote </span><span lang="EN" new="" style="margin: 0px; color: rgb(34, 34, 34); font-family: " times="">form alone does not lead to disease, and it is necessary to examine the presence of other mutations in the gene. While this mutation may be present as compound heterozygote along with other mutations in the rest of the exons in patients.</span></i></font><span style='margin: 0px; line-height: 150%; font-family: "Times New Roman",serif;'></span></p> <br> &nbsp; هایپرپلازی مادرزادی آدرنال, CAH , CYP21A2 , Cluster exon 6 21-Hydroxylase deficiency, CAH ,Congenital adrenal hyperplasia, CYP21A2 116 120 http://pejouhesh.sbmu.ac.ir/browse.php?a_code=A-10-3332-1&slc_lang=fa&sid=1 fahimeh baghbani فهیمه باغبانی fbaghbani@iauvaramin.ac.ir 100319475328460029146 100319475328460029146 Yes Varamin-Pishva branch, Islamic Azad University دانشگاه آزاد اسلامی واحد ورامین azadeh shojaei آزاده شجاعی a_shojaei2007@yahoo.com 100319475328460029147 100319475328460029147 No Iran University of Medical Sciences ، دانشگاه علوم پزشکی ایران neda asghari ندا اصغری neda.asghari.kollahi@gmail.com 100319475328460029148 100319475328460029148 No Varamin-Pishva branch, Islamic Azad University دانشگاه آزاد اسلامی واحد ورامین-