Kardiyovasküler Hastalıkların Tanısında Yeni Nesil Dizi Analizi Yöntemi ile Genetik Varyasyonların Tespitinin Önemi

GİRİŞ ve AMAÇ: Kardiyovasküler hastalıklar (KVH) geniş bir hastalık grubu olup, etiyopatogenezinde farklı risk faktörleri olmakla birlikte, genetik faktörler ayrı bir öneme sahiptir. Çalışmamızda, hedefli genlerin moleküler genetik analizinin KVH’da klinik tanıya hangi oranda katkı sağladığını belirlemeyi amaçladık. YÖNTEM ve GEREÇLER: KVH klinik tanısı ile takip edilen 38 hastada, periferik kandan DNA izolasyonu sonrasında 54 OMIM genini kapsayan hedefli panel kullanılarak, Illumina NextSeq550 sisteminde bu 54 genin analizi gerçekleştirildi. BULGULAR: Çalışmaya 23 erkek, 15 kadın olmak üzere dahil edilen hastaların yaş ortalaması kadınlarda 33.6, erkeklerde 32.8 olmak üzere tüm olgularda ortalama 33.1’di. 11 olguda (%28.9) 13 patojenik/olası patojenik varyasyon, 13 (%34.2) olguda 16 klinik önemi bilinmeyen varyasyon (VUS) saptadık. 6’sı patojenik/olası patojenik, 3’ü VUS olmak üzere toplam 9 varyasyon açık erişimli veri tabanlarında bugüne kadar rapor edilmemiş yeni varyasyondu. TARTIŞMA ve SONUÇ: KVH grubunda yeni nesil dizi analizi (NGS), çalışmamızda tanıya % 28.9 oranında bir katkı sağladı. NGS ile, nedeni belirlenemeyen kardiyovasküler hastalık bulgusu olan olgularda, çoklu gen analizi tanı oranlarını arttırmakta, tanı koyma süresini kısaltmaktadır.

The Importance of Detecting Genetic Variations with the New Generation Sequencing Method for the Diagnosis of Cardiovascular Diseases

INTRODUCTION: Cardiovascular diseases (CVD) are a large group of diseases and although there are different risk factors in their etiopathogenesis, genetic factors have a special importance. In our study, we aimed to determine the importance of contribution of molecular genetic analysis of targeted genes in clinical diagnosis of CVD. METHODS: Analysis was performed in the Illumina NextSeq550 system using a targeted panel consisting of 54 OMIM genes after DNA isolation from peripheral blood in 38 patients followed up with a clinical diagnosis of CVD. RESULTS: The average age of the patients included in the study, including 23 men and 15 women, was 33.6 in women, 32.8 in men, and 33.1 in all cases. We detected 13 pathogenic/likely pathogenic variations in 11 cases (28.9%), and 16 variations of unknown clinical significance (VUS) in 13 (34.2%) cases. A total of 9 variations, 6 of which were pathogenic/likely pathogenic, 3 of which were VUS, were the novel variations which were not reported in open access databases up to date. DISCUSSION AND CONCLUSION: The dignosis rate was 28.9% with next generation sequencing (NGS) method in our study in the CVD group. With NGS, in cases with unidentified cardiovascular disease findings, multiple gene analysis increases the diagnosis rates and shortens the diagnosis time.

Kaynakça

1. Genovesi S, Giussani M, Orlando A, Battaglino MG, Nava E, Parati G. Prevention of Cardiovascular Diseases in Children and Adolescents. High Blood Press Cardiovasc Prev 2019 Jun;26(3):191-197. doi: 10.1007/s40292-019-00316-6.

2. van Dijk EL, Auger H, Jaszczyszyn Y, Thermes C. Ten years of next-generation sequencing technology. Trends Genet 2014 Sep;30(9):418-26. doi: 10.1016/j.tig.2014.07.001.

3. Yohe S, Thyagarajan B. Review of Clinical Next-Generation Sequencing. Arch Pathol Lab Med 2017 Nov;141(11):1544-1557. doi: 10.5858/arpa.2016-0501-RA.

4. Nicora G, Limongelli I, Gambelli P, Memmi M, Malovini A, Mazzanti A, et al. CardioVAI: An automatic implementation of ACMG-AMP variant interpretation guidelines in the diagnosis of cardiovascular diseases. Hum Mutat 2018 Dec;39(12):1835-1846. doi: 10.1002/humu.23665.

5. Den Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, McGowan-Jordan J, et al. HGVS Recommendations for the Description of Sequence Variants: 2016 Update. Hum Mutat 2016;37(6): 564-9. doi: 10.1002/humu.22981.

6. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17(5): 405-24. doi: 10.1038/gim.2015.30.

7. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014 Jun 24;129(25 Suppl 2):S49-73. doi: 10.1161/01.cir.0000437741.48606.98.

8. Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M, Nichols M. Cardiovascular disease in Europe: epidemiological update 2016. Eur Heart J 2016 Nov 7;37(42):3232-3245. Epub 2016 Aug 14.

9. Schrage B, Geelhoed B, Niiranen TJ, Gianfagna F, Vishram-Nielsen JKK, Costanzo S, et al. Comparison of Cardiovascular Risk Factors in European Population Cohorts for Predicting Atrial Fibrillation and Heart Failure, Their Subsequent Onset, and Death. J Am Heart Assoc 2020 May 5;9(9):e015218. doi: 10.1161/JAHA.119.015218. Epub 2020 Apr 30.

10. Mohammed WJ, Al-Musawi BMS, Oberkanins C, Pühringer H. Molecular assessment of some cardiovascular genetic risk factors among Iraqi patients with ischemic heart diseases. Int J Health Sci (Qassim) 2018 May-Jun;12(3):44-50.

11. Weerakkody R, Ross D, Parry DA, Ziganshin B, Vandrovcova J, Gampawar P, et al. Targeted genetic analysis in a large cohort of familial and sporadic cases of aneurysm or dissection of the thoracic aorta. Genet Med 2018 Nov;20(11):1414-1422. doi: 10.1038/gim.2018.27.

12. Li Z, Zhou C, Tan L, Chen P, Cao Y, Li X, et al. A targeted sequencing approach to find novel pathogenic genes associated with sporadic aortic dissection. Sci China Life Sci 2018 Dec;61(12):1545-1553. doi: 10.1007/s11427-018-9382-0.

13. Hosen MJ, Van Nieuwerburgh F, Steyaert W, Deforce D, Martin L, Leftheriotis G, et al. Efficiency of exome sequencing for the molecular diagnosis of pseudoxanthoma elasticum. J Invest Dermatol 2015 Apr;135(4):992-998. doi: 10.1038/jid.2014.421.

14. Bertolini S, Pisciotta L, Fasano T, Rabacchi C, Calandra S. The study of familial hypercholesterolemia in Italy: A narrative review. Atheroscler Suppl 2017 Oct;29:1-10. doi: 10.1016/j.atherosclerosissup.2017.07.003.

15. Andrés-Ramos I, Alegría-Landa V, Gimeno I, Pérez-Plaza A, Rütten A, Kutzner H, et al. Cutaneous Elastic Tissue Anomalies. Am J Dermatopathol 2019;41:85–117.

Kaynak Göster

Kocaeli Tıp Dergisi
  • ISSN: 2147-0758
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 2012

6.6b3.7b

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