استفاده از روش توالی‌یابی اگزوم در شناسایی جهش‌های ژنتیکی کاردیومیوپاتی هایپرتروفیک و کاردیومیوپاتی اتساعی

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 کارشناسی ارشد، گروه ژنتیک، دانشکده‌ی علوم پایه، مؤسسه آموزش عالی آل طه، تهران، ایران

2 استادیار، گروه ژنتیک، دانشکده‌ی علوم پایه، مؤسسه آموزش عالی آل طه، تهران، ایران

3 دکتری تخصصی، مرکز قلب و عروق شهیدرجایی، دانشگاه علوم پزشکی ایران، تهران، ایران

4 استادیار، مرکز تحقیقات کاردیوژنتیک، مرکز قلب و عروق شهیدرجایی، دانشگاه علوم پزشکی ایران، تهران، ایران

چکیده

مقاله پژوهشی




مقدمه: کاردیومیوپاتی هایپرتروفیک و کاردیومیوپاتی اتساعی، عمدتاً با تظاهرات بالینی مختلف و در افراد با سابقه‌ی ژنتیکی پدیدار می‌شوند، در این حالت توالی‌یابی اگزوم امکان بررسی جامع از مناطق کدکننده‌ی پروتئین ژنوم را فراهم می‌کند و شناسایی انواع واریانت‌های نادر و بالقوه‌ی بیماری‌‌زا مرتبط با این شرایط را تسهیل می‌نماید. علاوه براین، داده‌‌های حاصل از توالی‌یابی اگزوم می‌تواند بینش گسترده‌تری را در مورد مکانیسم‌های مولکولی مؤثر در پاتوژنز کاردیومیوپاتی هایپرتروفیک و اتساعی ارایه دهد.
روش‌ها: نمونه‌ی خون از دو فرد بیمار از دو خانواده ایرانی دارای کاردیومیوپاتی هایپرتروفیک و کاردیومیوپاتی اتساعی و اعضای خانواده‌های آن‌ها جمع‌آوری گردید، سپس با استفاده از روش Salting out، نمونه‌ی DNA آن‌ها استخراج شد. نمونه‌ها جهت انجام توالی‌یابی اگزوم به شرکت ماکروژن کره جنوبی ارسال شدند و سپس داده خام در مرکز قلب و عروق شهید رجائی مورد تجزیه و تحلیل قرار گرفت. طراحی پرایمر و PCR برای واریانت‌های کاندید و همچنین توالی‌یابی سنگر برای بیماران و خانواده آن‌ها انجام شد.
یافته‌ها: در این مطالعه، دو واریانت گزارش شده‌ی مختلف، یکی در ژن  TPM1 (A:p.E156K< c.466G) و دیگری در ژنACTN2  (c.2648C>T:p.A883V)     در خانواده‌ی A (هردو هتروزیگوت) و یک واریانت گزارش شده در ژن (c.2218C>T:p.R740X)  در خانواده‌ی B (هموزیگوت) شناسایی شدند. جهش‌های یافته شده در بیماران تأیید و در اعضای خانواده‌ی سگرگیت شد.
نتیجه‌گیری: نتایج مطالعه‌ی حاضر نشان داد، جهش‌های ژن‌هایTPM1،ACTN2  و NRAP در خانواده‌های دارای افراد مبتلا به کاردیومیوپاتی می‌تواند در علت‌یابی بیماری و شناسایی افراد در معرض خطر خانواده، کمک‌کننده می‌باشد.

تازه های تحقیق

فاطمه اکبریان:  Google Scholar 

پریسا علی دوست سلیمی: Google Scholar

سمیرا کلائی نیا: Google Scholar

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

The Use of Exome Sequencing in Identifying Genetic Mutations of Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy

نویسندگان [English]

  • Dinazahra Mokhtari 1
  • Fatemeh Akbarian 2
  • Parisa Alidoost Salimi 3
  • Samira Kalayinia 4
1 MSc, Department of Genetics, School of Basic Sciences, Al Taha Institute of Higher Education, Tehran, Iran
2 Assistant Professor, Department of Genetics, School of Basic Sciences, Al Taha Institute of Higher Education, Tehran, Iran
3 PhD Candidate, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
4 Assistant Professor, Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
چکیده [English]

Background: Hypertrophic cardiomyopathy and dilated cardiomyopathy appear with diverse clinical manifestations and genetic history. Exome sequencing provides the possibility of a comprehensive examination of the protein-coding regions of the genome and the identification of rare and potentially pathogenic variants related to these conditions. Facilitates The data obtained from exome sequencing can provide a broader insight into the molecular mechanisms that affect the pathogenesis of hypertrophic and dilated cardiomyopathy.
Methods: Blood samples were collected from 2 patients and their families with Hypertrophic and Dilated Cardiomyopathy. Their DNA was extracted using the salting out method. Patient samples were sent to South Korea's Macrogen Company for exome sequencing and the raw data was analyzed at the Shahid Rajaei Heart and Vascular Center. Primer and PCR design for candidate variants and trench sequencing were done for patients and their families.
Findings: In this study, two different variants, one in TPM1 gene (c.466G>A:p.E156K) and another in ACTN2 gene (c.2648C>T:p.A883V), both in family A and one variant in NRAP gene (c.2218C>T:p.R740X) was identified in family B. Mutations found in patients were confirmed and segregated in family members.
Conclusion: The results of the present study show that examining TPM1, ACTN2, and NRAP genes in families with people with cardiomyopathy can help diagnose the cause of the disease and identifying people at risk in the family.

کلیدواژه‌ها [English]

  • Cardiomyopathies
  • Exome sequencing
  • Mutation
  • Heart diseases
  • Iran
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