بررسی جهش در اگزون‌های 8 و 3 ژن 1A3SLC و اگزون‌های 4 و 10 ژن 9A7 SLC در بیماران مبتلا به سیتینوری در ایران

نوع مقاله : Original Article(s)

نویسندگان

1 دانشجوی کارشناسی ارشد، مرکز تحقیقات بیماری‌های ارثی کودکان و گروه ژنتیک و بیولوژی مولکولی، دانشکده‌ی پزشکی و کمیته‌ی تحقیقات دانشجویی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

2 استادیار، گروه اورولوژی، دانشکده‌ی پزشکی و مرکز تحقیقات پیوند کلیه، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

3 دانشیار، مرکز تحقیقات بیماری‌های ارثی کودکان و گروه ژنتیک و بیولوژی مولکولی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

4 دانشجوی دکتری، مرکز تحقیقات گیاهان دارویی رازی، دانشگاه علوم پزشکی لرستان، خرم‌آباد، ایران

5 استادیار، مرکز تحقیقات بیماری‌های ارثی کودکان و گروه ژنتیک و بیولوژی مولکولی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

چکیده

مقدمه: سسیستینوری یکی از اولین اختلالات متابولیسمی شناخته شده می‌باشد که با افزایش ترشح سیستین، آرژنین، لیزین و اورنیتین به درون ادرار مشخص می‌شود. دو ژن در ارتباط با بیماری شناخته شده است: ژن 1A3SLC (3/16p2) کد کننده‌ی زیر واحد سنگین rBAT، متعلق به ترانسپورتر کلیوی +,0b و ژن 9A7SLC (1/13q19) که زیر واحد سبک ترانسپورتر را کدگذاری می‌کند. بیماران با دو جهش در ژن 1A3SLC به عنوان نوع A، بیماران با دو جهش در ژن 9A7SLC به عنوان نوع B شناخته می‌شوند. بیماران با سیستینوری نوع AB دارای یک جهش در ژن 1A3SLC و یک جهش در ژن 9A7SLC می‌باشند. با وجود توزیع اختصاصی جهش در جمعیت‌های خاص، مطالعات محدودی در خاور میانه صورت گرفته است. این مطالعه نتایج بررسی ژنتیکی در بیماران مبتلا به سیستینوری در ایران را ارایه می‌دهد.روش‌ها: 30 بیمار تحت عمل جراحی برداشت سنگ کلیه، توسط پزشک متخصص اورولوژیست با تشخیص سنگ‌ها‌ی سیستینی انتخاب شدند. بیماران برای تعیین جهش، با استفاده از روش‌های ARMS (Amplification refractory mutation system) و PCR-RFLP (Polymerase chain reaction-Restriction fragment length polymorphism) مورد بررسی قرار گرفتند.یافته‌ها: در مجموع چند واریانت اعم از بد معنی، پلی‌مورفیسم، هم‌معنی و واریانت اینترونی یافت شدند؛ اما جهش‌های شایع مطالعات دیگر، در بیماران این مطالعه یافت نشدند.نتیجه‌گیری: شاید بتوان این مطالعه را تأییدی بر اثر نژادی روی توزیع جهش‌ها در بیماری سیستینوری دانست. امید آن می‌رود که این مطالعه بتواند در درک ژنتیک مولکولی بیماران سیستینوری در ایران روشنگر باشد. 

کلیدواژه‌ها

عنوان مقاله [English]

Detection of Mutation in Exons 3 and 8 of SLC3A1 and Exons 4 and 10 of SLC7A9 Genes in Patients with Cystinuria in Iran

نویسندگان [English]

  • Leila Koulivand 1
  • Mehrdad Mohammadi 2
  • Rasoul Salehi 3
  • Behrouz Ezatpour 4
  • Majid Kheirollahi 5
1 MSc Student, Pediatrics Inherited Diseases Research Center AND Department of Genetics and Molecular Biology, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
2 Assistant Professor, Department of Urology, School of Medicine AND Urology and Kidney Transplantation Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3 Associate Professor, Pediatrics Inherited Diseases Research Center AND Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
4 PhD Student, Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
5 Assistant Professor, Pediatrics Inherited Diseases Research Center AND Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
چکیده [English]

Background: Cystinuria, one of the first diagnosed inborn errors of metabolism, recognized by hyperexcretion of cystine, lysine, ornithine and arginine into the urine. So far, two genes associated with cystinuria have been identified: SLC3A1 (2p16.3) that encodes the heavy subunit rBAT of the renal b<sup>0,+ transporter and SLC7A9 (19q13.1), which encodes the light subunit b<sup>0,+AT. Patients with type A cystinuria have two SLC3A1 mutations, whereas patients with type B have two SLC7A9 mutations and finally patients with type AB have one mutation in each gene. Considering the population-specific distribution of mutations in disease, limited studies on the genetic bases of the cystinuria have been done in Middle East. This research presents the results of mutation analysis on patients with cystinuria in Iran.Methods: Thirty unrelated patients with cystinuria operated to remove kidney stones were screened by urologist .The patients were analyzed for mutation using amplification refractory mutation system (ARMS) and polymerase chain reaction-Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods.Findings: We found some variations including missense mutations, polymorphism and intron variant, but the most frequent mutations, M467T and also T216M and R333W, were not detected in our patients.Conclusion: Our research may confirm the ethnic distribution of mutations in cystinuria and this study can expand our concept of the genetic basis of cystinuria in Iranian patients. 

کلیدواژه‌ها [English]

  • Cystinuria
  • Mutation
  • Iran

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مجله دانشکده پزشکی اصفهان
دوره 32، شماره 293 - شماره پیاپی 293
مرداد و شهریور 1393
صفحه 1073-1080

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سابقه مقاله

  • تاریخ دریافت: 05 اردیبهشت 1393
  • تاریخ بازنگری: 12 آبان 1403
  • تاریخ پذیرش: 17 فروردین 1401

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