The utility of exome sequencing in diagnosis of hereditary diseases
Abstract
Identification of the genetic cause of a hereditary disease is a necessary step in the differential diagnosis, because plays an important role in evaluation of genetic risk, and in some cases also helps to determine the method of treatment, for example, for some hereditary metabolic diseases. The subsequent choice of molecular genetic testing method can be very difficult due to the presence of a number of advantages and limitations for each of these approaches. Methods of molecular genetic testing in order to identify the genetic causes of a hereditary disease, first of all, differ in diagnostic efficiency, time and cost of the study. In addition, the characteristics of different methods can also vary significantly for different groups of genetic diseases. Using the wrong method can significantly increase the time and cost of diagnosis. Recently, several data indicate that one of the next generation sequencing (NGS) methods - exome sequencing - has high efficacy for identification of the genetic cause of certain groups of hereditary diseases. Exome sequencing provides information about changes in gene coding regions - exons. A trio exome sequencing in families further increases the effectiveness of such analysis. The article describes the examples of clinical and financial feasibility of exome sequencing to identify the genetic cause of a hereditary disease. Such cases include: rare genetic diseases, heterogeneous diseases in children 0-3 years old, recently established connection of a gene with a disease, testing after negative results of other studies, for prenatal diagnosis, for financial reasons.
About the Authors
E. G. Okuneva
Genotek Ltd
Russian Federation
Russian Federation
A. A. Kozina
Pirogov Russian National Research Medical University; Institute of Biomedical Chemistry
Russian Federation
Russian Federation
N. V. Baryshnikova
Genotek Ltd; Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
A. Yu. Krasnenko
Genotek Ltd
Russian Federation
Russian Federation
O. I. Klimchuk
Genotek Ltd
Russian Federation
Russian Federation
I. F. Stetsenko
Genotek Ltd
Russian Federation
Russian Federation
N. A. Plotnikov
Genotek Ltd
Russian Federation
Russian Federation
E. I. Surkova
Genotek Ltd
Russian Federation
Russian Federation
V. V. Ilinsky
Genotek Ltd
Russian Federation
Russian Federation
References
1. Choi M., Scholl U.I., Ji W., Liu T., Tikhonova I.R., Zumbo P. et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proceedings of the National Academy of Sciences USA 2009; 106(45): 19096-19101. doi: 10.1073/pnas.0910672106.
2. Ng S.B., Turner E.H., Robertson P.D., Flygare S.D., Bigham A.W., Lee C. et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 2009; 461(7261): 272-276. doi: 10.1038/nature08250.
3. Ng S.B., Buckingham K.J., Lee C., Bigham A.W., Tabor H.K., Dent K.M. et al. Exome sequencing identifies the cause of a mendelian disorder. Nature Genetics 2010; 42(1): 30-35. doi: 10.1038/ng.499.
4. Farlow J.L., Robak L.A., Hetrick K., Bowling K., Boerwinkle E., Coban-Akdemir Z.H. et al. Whole-Exome Sequencing in Familial Parkinson Disease. JAMA Neurology 2016; 73(1): 68-75. doi: 10.1001/jamaneurol.2015.3266.
5. Jansen I.E., Ye H., Heetveld S., Lechler M.C., Michels H., Seinstra R.I. et al. Discovery and functional prioritization of Parkinson’s disease candidate genes from large-scale whole exome sequencing. Genome Biology 2017; 18(1): 22. doi: 10.1186/s13059-017-1147-9.
6. Wang L., Zhang J., Chen N., Wang L., Zhang F., Ma Z. et al. Application of Whole Exome and Targeted Panel Sequencing in the Clinical Molecular Diagnosis of 319 Chinese Families with Inherited Retinal Dystrophy and Comparison Study. Genes (Basel) 2018; 9(7): E360. doi: 10.3390/genes9070360.
7. Dillon O.J., Lunke S., Stark Z., Yeung A., Thorne N., Gaff C. et al. Exome sequencing has higher diagnostic yield compared to simulated disease-specific panels in children with suspected monogenic disorders. Eur J Hum Genet 2018; 26(5): 644-651. doi:10.1038/s41431-018-0099-1.
8. Sawyer S.L., Hartley T., Dyment D.A., Beaulieu C.L., Schwartzentruber J., Smith A. et al. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clinical Genetics 2016; 89(3): 275-284. doi: 10.1111/cge.12654.
9. Clark M.M., Stark Z., Farnaes L., Tan T.Y., White S.M., Dimmock D. et al. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genomic Medicine 2018; 3: 16. doi: 10.1038/s41525-018-0053-8.
10. Rodriguez-Revenga L., Iranzo P., Badenas C., Puig S., Carrió A., Milà M. A novel elastin gene mutation resulting in an autosomal dominant form of cutis laxa. Archives of Dermatology 2004; 140(9): 1135-1139.
11. Дадали Е.Л., Гинтер Е.К., Поляков А.В. Генетическая гетерогенность и некоторые другие проблемы, осложняющие диагностику наследственных болезней нервной системы. Нервно-мышечные болезни 2012; (1): 11-19.
12. McClellan J., King M.C. Genetic heterogeneity in human disease. Cell 2010; 141(2): 210-217. doi: 10.1016/j.cell.2010.03.032.
13. Wang X., Wei X., Thijssen B., Das J., Lipkin S.M., Yu H. Three-dimensional reconstruction of protein networks provides insight into human genetic disease. Nature Biotechnology 2012; 30(2): 159-64. doi: 10.1038/nbt.2106.
14. Guo Y., Wei X., Das J., Grimson A., Lipkin S.M., Clark A.G. et al. Dissecting disease inheritance modes in a three-dimensional protein network challenges the “guilt-by-association” principle. American Journal of Human Genetics 2013; 93(1): 78-89. doi: 10.1016/j.ajhg.2013.05.022.
15. Hartong D.T., Berson E.L., Dryja T.P. Retinitis pigmentosa. Lancet 2006;368(9549):1795-809.
16. Monies D., Alhindi H.N., Almuhaizea M.A., Abouelhoda M., Alazami A.M., Goljan E. et al. A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies. Human Genomics 2016; 10(1): 32.
17. Clark M.M., Stark Z., Farnaes L., Tan T.Y., White S.M., Dimmock D. et al. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genomic Medicine 2018; 3: 16. doi: 10.1038/s41525-018-0053-8.
18. Hickey E.J., Mehta R., Elmi M., Asoh K., McCrindle B.W., Williams W.G. et al. Survival implications: hypertrophic cardiomyopathy in Noonan syndrome. Congenital Heart Disease 2011; 6(1): 41-47. doi: 10.1111/j.1747-0803.2010.00465.x.
19. Waldrop M.A., Pastore M., Schrader R., Sites E., Bartholomew D., Tsao C.Y. et al. Diagnostic Utility of Whole Exome Sequencing in the Neuromuscular Clinic. Neuropediatrics 2019; 50(2): 96-102. doi: 10.1055/s-0039-1677734.
20. Thiel C., Rind N., Popovici D., Hoffmann G.F., Hanson K., Conway R.L. et al. Improved diagnostics lead to identification of three new patients with congenital disorder of glycosylation-Ip. Hum Mutat 2012; 33(3): 485-487. doi:10.1002/humu.22019.
21. Rind N., Schmeiser V., Thiel C., Absmanner B., Lübbehusen J., Hocks J. et al. A severe human metabolic disease caused by deficiency of the endoplasmatic mannosyltransferase hALG11 leads to congenital disorder of glycosylation-Ip. Human Molecular Genetics 2010; 19(8): 1413-1424. doi: 10.1093/hmg/ddq016.
22. Al Teneiji A., Bruun T.U., Sidky S., Cordeiro D., Cohn R.D., Mendoza-Londono R. et al. Phenotypic and genotypic spectrum of congenital disorders of glycosylation type I and type II. Molecular Genetics and Metabolism 2017; 120(3): 235-242. doi: 10.1016/j.ymgme.2016.12.014.
23. Pereira A.G., Bahi-Buisson N., Barnerias C., Boddaert N., Nabbout R., de Lonlay P. et al. Epileptic spasms in congenital disorders of glycosylation. Epileptic Disorders 2017; 19(1): 15-23. doi: 10.1684/epd.2017.0901.
24. Regal L., van Hasselt P.M., Foulquier F., Cuppen I., Prinsen H., Jansen K. et al. ALG11-CDG: Three novel mutations and further characterization of the phenotype. Molecular Genetics and Metabolism Reports 2014; 2: 16-19. doi: 10.1016/j.ymgmr.2014.11.006.
25. Haanpää M.K., Ng B.G., Gallant N.M., Singh K.E., Brown C., Kimonis V. et al. ALG11-CDG syndrome: Expanding the phenotype. American Journal of Medical Genetics Part A 2019; 179(3): 498-502. doi: 10.1002/ajmg.a.61046.
26. Ortiz A., Germain D.P., Desnick R.J., Politei J., Mauer M., Burlina A. et al. Fabry disease revisited: Management and treatment recommendations for adult patients. Molecular Genetics and Metabolism 2018; 123(4): 416-427.
27. Zhang S., Lei C., Wu J., Sun H., Yang Y., Zhang Y. et al. A retrospective study of cytogenetic results from amniotic fluid in 5328 fetuses with abnormal obstetric sonographic findings. Journal of Ultrasound Medicine 2017; 36(9): 1809-1817. doi: 10.1002/jum.14215.
28. Monaghan K.G., Leach N.T., Pekarek D., Prasad P., Rose N.C.; ACMG Professional Practice and Guidelines Committee. The use of fetal exome sequencing in prenatal diagnosis: a points to consider document of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine 2020. doi: 10.1038/s41436-019-0731-7.
29. Sakai L.Y., Keene D.R., Renard M., De Backer J. FBN1: The disease-causing gene for Marfan syndrome and other genetic disorders. Gene 2016; 591(1): 279-291. doi: 10.1016/j.gene.2016.07.033.
30. Tran Mau-Them F., Moutton S., Racine C., Vitobello A., Bruel A.L., Nambot S. et al. Second-tier trio exome sequencing after negative solo clinical exome sequencing: an efficient strategy to increase diagnostic yield and decipher molecular bases in undiagnosed developmental disorders. Hum Genet 2020. doi:10.1007/s00439-020-02178-8.
Review
For citations:
Okuneva E.G., Kozina A.A., Baryshnikova N.V., Krasnenko A.Yu., Klimchuk O.I., Stetsenko I.F., Plotnikov N.A., Surkova E.I., Ilinsky V.V. The utility of exome sequencing in diagnosis of hereditary diseases. Medical Genetics. 2020;19(12):18-24. (In Russ.)
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