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Next-Generation Sequencing Reveals Novel Genetic Variants for Dilated Cardiomyopathy in Pediatric Chinese Patients

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Abstract

Dilated cardiomyopathy (DCM) is a myocardial disease characterized by bilateral or left ventricular cardiac dilation and systolic dysfunction that can lead to heart failure and sudden cardiac death in children. Many studies have focused on genetic variation in DCM-related genes in adult populations; however, the mutational landscape in pediatric DCM patients remains undetermined, especially in the Chinese population. We applied next-generation sequencing (NGS) technology to genetically analyze 46 pediatric DCM patients to reveal genotype–phenotype correlations. Our results indicated DCM-associated pathogenic mutations in 10 genes related to the structure or function of the sarcomere, desmosome, and cytoskeleton. We also identified 6 pathogenic mutations (5 novel) in the Titin (TTN) gene that resulted in truncated TTN variants in 6 (13%) out of 46 patients. Correlations between TTN mutations and clinical outcomes were assessed. Our data indicate that one-third of pediatric DCM cases are caused by genetic mutations. The role of TTN variants should not be underestimated in pediatric DCM and age-dependent pathogenic penetrance of these mutations should be considered for familial DCM cases. We argue that genetic testing of DCM cases is valuable for predicting disease severity, prognosis, and recurrence risk, and for screening first-degree relatives.

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Data Availability

The data and materials are available upon request.

Code Availability

N/A.

Abbreviations

ACMG:

American College of Medical Genetics and Genomics

ALT:

Alanine transaminase

AST:

Aspartate transaminase

CT:

Computed tomography

DCM:

Dilated cardiomyopathy

FLNC :

Filamin C

HGMD:

Human Gene Mutation Database

LVEDD:

Left ventricular end-diastolic diameter

LVEF:

Left ventricular ejection fraction

LVNC:

Left ventricular noncompaction

MYH7 :

β-Myosin heavy chain

NEXN :

Nexilin F-actin binding protein

NKX2-5 :

NK2 homeobox 5

NGS:

Next generation sequencing

NT-proBNP:

N-terminal pro-brain-natriuretic peptide

PRDM16 :

Positive regulatory domain16

RBM20 :

RNA-binding protein20

TNNI3 :

Troponin I3

TNNT2 :

Troponin T2

TTN :

Titin

VCL :

Vinculin

WES:

Whole-exome sequencing

References

  1. Taylor MR, Carniel E, Mestroni L (2006) Cardiomyopathy, familial dilated. Orphanet J Rare Dis 1:27. https://doi.org/10.1186/1750-1172-1-27

    Article  PubMed  PubMed Central  Google Scholar 

  2. Puggia I, Merlo M, Barbati G, Rowland TJ, Stolfo D, Gigli M, Ramani F, Di Lenarda A, Mestroni L, Sinagra G (2016) Natural history of dilated cardiomyopathy in children. J Am Heart Assoc 5(7):12. https://doi.org/10.1161/jaha.116.003450

    Article  CAS  Google Scholar 

  3. Nugent AW, Daubeney PE, Chondros P, Carlin JB, Cheung M, Wilkinson LC, Davis AM, Kahler SG, Chow CW, Wilkinson JL, Weintraub RG (2003) The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med 348(17):1639–1646. https://doi.org/10.1056/NEJMoa021737

    Article  PubMed  Google Scholar 

  4. Wilkinson JD, Sleeper LA, Alvarez JA, Bublik N, Lipshultz SE (2008) The pediatric cardiomyopathy registry: 1995–2007. Prog Pediatr Cardiol 25(1):31–36. https://doi.org/10.1016/j.ppedcard.2007.11.006

    Article  PubMed  PubMed Central  Google Scholar 

  5. Dellefave L, McNally EM (2010) The genetics of dilated cardiomyopathy. Curr Opin Cardiol 25(3):198–204. https://doi.org/10.1097/HCO.0b013e328337ba52

    Article  PubMed  PubMed Central  Google Scholar 

  6. Akinrinade O, Ollila L, Vattulainen S, Tallila J, Gentile M, Salmenperä P, Koillinen H, Kaartinen M, Nieminen MS, Myllykangas S, Alastalo TP, Koskenvuo JW, Heliö T (2015) Genetics and genotype-phenotype correlations in Finnish patients with dilated cardiomyopathy. Eur Heart J 36(34):2327–2337. https://doi.org/10.1093/eurheartj/ehv253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Merlo M, Pivetta A, Pinamonti B, Stolfo D, Zecchin M, Barbati G, Di Lenarda A, Sinagra G (2014) Long-term prognostic impact of therapeutic strategies in patients with idiopathic dilated cardiomyopathy: changing mortality over the last 30 years. Eur J Heart Fail 16(3):317–324. https://doi.org/10.1002/ejhf.16

    Article  CAS  PubMed  Google Scholar 

  8. Jefferies JL, Towbin JA (2010) Dilated cardiomyopathy. Lancet (London, England) 375(9716):752–762. https://doi.org/10.1016/s0140-6736(09)62023-7

    Article  Google Scholar 

  9. Long PA, Larsen BT, Evans JM, Olson TM (2015) Exome sequencing identifies pathogenic and modifier mutations in a child with sporadic dilated cardiomyopathy. J Am Heart Assoc 4(12):12. https://doi.org/10.1161/jaha.115.002443

    Article  CAS  Google Scholar 

  10. Long PA, Zimmermann MT, Kim M, Evans JM, Xu X, Olson TM (2016) De novo RRAGC mutation activates mTORC1 signaling in syndromic fetal dilated cardiomyopathy. Hum Genet 135(8):909–917. https://doi.org/10.1007/s00439-016-1685-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Simpson S, Edwards J, Ferguson-Mignan TF, Cobb M, Mongan NP, Rutland CS (2015) Genetics of human and canine dilated cardiomyopathy. Int J Genomics 2015:204823. https://doi.org/10.1155/2015/204823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pérez-Serra A, Toro R, Sarquella-Brugada G, de Gonzalo-Calvo D, Cesar S, Carro E, Llorente-Cortes V, Iglesias A, Brugada J, Brugada R, Campuzano O (2016) Genetic basis of dilated cardiomyopathy. Int J Cardiol 224:461–472. https://doi.org/10.1016/j.ijcard.2016.09.068

    Article  PubMed  Google Scholar 

  13. Watkins H, Ashrafian H, Redwood C (2011) Inherited cardiomyopathies. N Engl J Med 364(17):1643–1656. https://doi.org/10.1056/NEJMra0902923

    Article  CAS  PubMed  Google Scholar 

  14. Jensen MK, Havndrup O, Christiansen M, Andersen PS, Diness B, Axelsson A, Skovby F, Køber L, Bundgaard H (2013) Penetrance of hypertrophic cardiomyopathy in children and adolescents: a 12-year follow-up study of clinical screening and predictive genetic testing. Circulation 127(1):48–54. https://doi.org/10.1161/circulationaha.111.090514

    Article  PubMed  Google Scholar 

  15. Precone V, Del Monaco V, Esposito MV, De Palma FD, Ruocco A, Salvatore F, D’Argenio V (2015) Cracking the code of human diseases using next-generation sequencing: applications. Chall Perspect 2015:161648. https://doi.org/10.1155/2015/161648

    Article  CAS  Google Scholar 

  16. Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, Conner L, DePalma SR, McDonough B, Sparks E, Teodorescu DL, Cirino AL, Banner NR, Pennell DJ, Graw S, Merlo M, Di Lenarda A, Sinagra G, Bos JM, Ackerman MJ, Mitchell RN, Murry CE, Lakdawala NK, Ho CY, Barton PJ, Cook SA, Mestroni L, Seidman JG, Seidman CE (2012) Truncations of titin causing dilated cardiomyopathy. N Engl J Med 366(7):619–628. https://doi.org/10.1056/NEJMoa1110186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pettersen MD, Du W, Skeens ME, Humes RA (2008) Regression equations for calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: an echocardiographic study. J Am Soc Echocardiogr 21(8):922–934. https://doi.org/10.1016/j.echo.2008.02.006

    Article  PubMed  Google Scholar 

  18. Daubeney PE, Nugent AW, Chondros P, Carlin JB, Colan SD, Cheung M, Davis AM, Chow CW, Weintraub RG (2006) Clinical features and outcomes of childhood dilated cardiomyopathy: results from a national population-based study. Circulation 114(24):2671–2678. https://doi.org/10.1161/circulationaha.106.635128

    Article  PubMed  Google Scholar 

  19. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, Garimella K, Altshuler D, Gabriel S, Daly M, DePristo MA (2010) The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 20(9):1297–1303. https://doi.org/10.1101/gr.107524.110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, Philippakis AA, del Angel G, Rivas MA, Hanna M, McKenna A, Fennell TJ, Kernytsky AM, Sivachenko AY, Cibulskis K, Gabriel SB, Altshuler D, Daly MJ (2011) A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet 43(5):491–498. https://doi.org/10.1038/ng.806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL (2015) 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 17(5):405–424. https://doi.org/10.1038/gim.2015.30

    Article  PubMed  PubMed Central  Google Scholar 

  22. Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dobbels F, Kirk R, Rahmel AO, Hertz MI (2011) The registry of the international society for heart and lung transplantation: twenty-eighth adult heart transplant report-2011. J Heart Lung Transplant 30(10):1078–1094. https://doi.org/10.1016/j.healun.2011.08.003

    Article  PubMed  Google Scholar 

  23. McNally EM, Golbus JR, Puckelwartz MJ (2013) Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Investig 123(1):19–26. https://doi.org/10.1172/JCI62862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Martinez-Selles M, Doughty RN, Poppe K, Whalley GA, Earle N, Tribouilloy C, McMurray JJ, Swedberg K, Kober L, Berry C, Squire I (2012) Meta-Analysis Global Group In Chronic Heart, Gender and survival in patients with heart failure: interactions with diabetes and aetiology. Results from the MAGGIC individual patient meta-analysis. Eur J Heart Fail 14(5):473–479. https://doi.org/10.1172/jci62862

    Article  PubMed  Google Scholar 

  25. Halliday BP, Gulati A, Ali A, Newsome S, Lota A, Tayal U, Vassiliou VS, Arzanauskaite M, Izgi C, Krishnathasan K, Singhal A, Chiew K, Gregson J, Frenneaux MP, Cook SA, Pennell DJ, Collins P, Cleland JGF, Prasad SK (2018) Sex- and age-based differences in the natural history and outcome of dilated cardiomyopathy. Eur J Heart Fail 20(10):1392–1400. https://doi.org/10.1002/ejhf.1216

    Article  PubMed  Google Scholar 

  26. Zhao Y, Feng Y, Zhang YM, Ding XX, Song YZ, Zhang AM, Liu L, Zhang H, Ding JH, Xia XS (2015) Targeted next-generation sequencing of candidate genes reveals novel mutations in patients with dilated cardiomyopathy. Int J Mol Med 36(6):1479–1486. https://doi.org/10.3892/ijmm.2015.2361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Pinto YM, Elliott PM, Arbustini E, Adler Y, Anastasakis A, Böhm M, Duboc D, Gimeno J, de Groote P, Imazio M, Heymans S, Klingel K, Komajda M, Limongelli G, Linhart A, Mogensen J, Moon J, Pieper PG, Seferovic PM, Schueler S, Zamorano JL, Caforio AL, Charron P (2016) Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J 37(23):1850–1858. https://doi.org/10.1093/eurheartj/ehv727

    Article  PubMed  Google Scholar 

  28. Ware SM, Wilkinson JD, Tariq M, Schubert JA, Sridhar A, Colan SD, Shi L, Canter CE, Hsu DT, Webber SA, Dodd DA, Everitt MD, Kantor PF, Addonizio LJ, Jefferies JL, Rossano JW, Pahl E, Rusconi P, Chung WK, Lee T, Towbin JA, Lal AK, Bhatnagar S, Aronow B, Dexheimer PJ, Martin LJ, Miller EM, Sleeper LA, Razoky H, Czachor J, Lipshultz SE (2021) Pediatric Cardiomyopathy Registry study, genetic causes of cardiomyopathy in children: first results from the pediatric cardiomyopathy genes study. J Am Heart Assoc 10(9):7731. https://doi.org/10.1161/JAHA.120.017731

    Article  Google Scholar 

  29. Haggerty CM, Damrauer SM, Levin MG, Birtwell D, Carey DJ, Golden AM, Hartzel DN, Hu Y, Judy R, Kelly MA, Kember RL, Lester Kirchner H, Leader JB, Liang L, McDermott-Roe C, Babu A, Morley M, Nealy Z, Person TN, Pulenthiran A, Small A, Smelser DT, Stahl RC, Sturm AC, Williams H, Baras A, Margulies KB, Cappola TP, Dewey FE, Verma A, Zhang X, Correa A, Hall ME, Wilson JG, Ritchie MD, Rader DJ, Murray MF, Fornwalt BK, Arany Z (2019) Genomics-first evaluation of heart disease associated with titin-truncating variants. Circulation 140(1):42–54. https://doi.org/10.1161/CIRCULATIONAHA.119.039573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fatkin D, Huttner IG (2017) Titin-truncating mutations in dilated cardiomyopathy: the long and short of it. Curr Opin Cardiol 32(3):232–238. https://doi.org/10.1097/hco.0000000000000382

    Article  PubMed  Google Scholar 

  31. Ellepola CD, Knight LM, Fischbach P, Deshpande SR (2018) Genetic testing in pediatric cardiomyopathy. Pediatr Cardiol 39(3):491–500. https://doi.org/10.1007/s00246-017-1779-2

    Article  PubMed  Google Scholar 

  32. Vasilescu C, Ojala TH, Brilhante V, Ojanen S, Hinterding HM, Palin E, Alastalo TP, Koskenvuo J, Hiippala A, Jokinen E, Jahnukainen T, Lohi J, Pihkala J, Tyni TA, Carroll CJ, Suomalainen A (2018) Genetic basis of severe childhood-onset cardiomyopathies. J Am Coll Cardiol 72(19):2324–2338. https://doi.org/10.1016/j.jacc.2018.08.2171

    Article  CAS  PubMed  Google Scholar 

  33. Dai G, Pu Z, Cheng X, Yin J, Chen J, Xu T, Zhang H, Li Z, Chen X, Chen J, Qin Y, Yang S (2019) Whole-exome sequencing reveals novel genetic variation for dilated cardiomyopathy in pediatric Chinese patients. Pediatr Cardiol 40(5):950–957. https://doi.org/10.1007/s00246-019-02096-1

    Article  PubMed  Google Scholar 

  34. Zaklyazminskaya E, Mikhailov V, Bukaeva A, Kotlukova N, Povolotskaya I, Kaimonov V, Dombrovskaya A, Dzemeshkevich S (2019) Low mutation rate in the TTN gene in paediatric patients with dilated cardiomyopathy—a pilot study. Sci Rep 9(1):16409. https://doi.org/10.1038/s41598-019-52911-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Jansweijer JA, Nieuwhof K, Russo F, Hoorntje ET, Jongbloed JD, Lekanne Deprez RH, Postma AV, Bronk M, van Rijsingen IA, de Haij S, Biagini E, van Haelst PL, van Wijngaarden J, van den Berg MP, Wilde AA, Mannens MM, de Boer RA, van Spaendonck-Zwarts KY, van Tintelen JP, Pinto YM (2017) Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy. Eur J Heart Fail 19(4):512–521. https://doi.org/10.1002/ejhf.673

    Article  CAS  PubMed  Google Scholar 

  36. Felkin LE, Walsh R, Ware JS, Yacoub MH, Birks EJ, Barton PJ, Cook SA (2016) Recovery of cardiac function in cardiomyopathy caused by titin truncation. JAMA Cardiol 1(2):234–235. https://doi.org/10.1001/jamacardio.2016.0208

    Article  PubMed  PubMed Central  Google Scholar 

  37. Anderson JL, Christensen GB, Escobar H, Horne BD, Knight S, Jacobs V, Afshar K, Hebl VB, Muhlestein JB, Knowlton KU, Carlquist JF, Nadauld LD (2020) Discovery of TITIN gene truncating variant mutations and 5-year outcomes in patients with nonischemic dilated cardiomyopathy. Am J Cardiol 137:97–102. https://doi.org/10.1016/j.amjcard.2020.09.026

    Article  CAS  PubMed  Google Scholar 

  38. Tobita T, Nomura S, Fujita T, Morita H, Asano Y, Onoue K, Ito M, Imai Y, Suzuki A, Ko T, Satoh M, Fujita K, Naito AT, Furutani Y, Toko H, Harada M, Amiya E, Hatano M, Takimoto E, Shiga T, Nakanishi T, Sakata Y, Ono M, Saito Y, Takashima S, Hagiwara N, Aburatani H, Komuro I (2018) Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling. Sci Rep 8(1):1998. https://doi.org/10.1038/s41598-018-20114-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Verdonschot JAJ, Hazebroek MR, Derks KWJ, Barandiaran Aizpurua A, Merken JJ, Wang P, Bierau J, van den Wijngaard A, Schalla SM, Abdul Hamid MA, van Bilsen M, van Empel VPM, Knackstedt C, Brunner-La Rocca HP, Brunner HG, Krapels IPC, Heymans SRB (2018) Titin cardiomyopathy leads to altered mitochondrial energetics, increased fibrosis and long-term life-threatening arrhythmias. Eur Heart J 39(10):864–873. https://doi.org/10.1093/eurheartj/ehx808

    Article  CAS  PubMed  Google Scholar 

  40. Kayvanpour E, Sedaghat-Hamedani F, Amr A, Lai A, Haas J, Holzer DB, Frese KS, Keller A, Jensen K, Katus HA, Meder B (2017) Genotype-phenotype associations in dilated cardiomyopathy: meta-analysis on more than 8000 individuals. Clin Res Cardiol 106(2):127–139. https://doi.org/10.1007/s00392-016-1033-6

    Article  CAS  PubMed  Google Scholar 

  41. Watanabe T, Kimura A, Kuroyanagi H (2018) Alternative splicing regulator RBM20 and cardiomyopathy. Front Mol Biosci 5:105. https://doi.org/10.3389/fmolb.2018.00105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Miszalski-Jamka K, Jefferies JL, Mazur W, Głowacki J, Hu J, Lazar M, Gibbs RA, Liczko J, Kłyś J, Venner E, Muzny DM, Rycaj J, Białkowski J, Kluczewska E, Kalarus Z, Jhangiani S, Al-Khalidi H, Kukulski T, Lupski JR, Craigen WJ, Bainbridge MN (2017) Novel genetic triggers and genotype-phenotype correlations in patients with left ventricular noncompaction, circulation. Cardiovasc Genet 10(4):20. https://doi.org/10.1161/circgenetics.117.001763

    Article  Google Scholar 

  43. Parikh VN, Caleshu C, Reuter C, Lazzeroni LC, Ingles J, Garcia J, McCaleb K, Adesiyun T, Sedaghat-Hamedani F, Kumar S, Graw S, Gigli M, Stolfo D, Dal Ferro M, Ing AY, Nussbaum R, Funke B, Wheeler MT, Hershberger RE, Cook S, Steinmetz LM, Lakdawala NK, Taylor MRG, Mestroni L, Merlo M, Sinagra G, Semsarian C, Meder B, Judge DP, Ashley E (2019) Regional variation in RBM20 causes a highly penetrant arrhythmogenic cardiomyopathy. Circ Heart Fail 12(3):e005371. https://doi.org/10.1161/CIRCHEARTFAILURE.118.005371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hoedemaekers YM, Cohen-Overbeek TE, Frohn-Mulder IM, Dooijes D, Majoor-Krakauer DF (2013) Prenatal ultrasound diagnosis of MYH7 non-compaction cardiomyopathy. Ultrasound Obstet Gynecol 41(3):336–339

    Article  CAS  PubMed  Google Scholar 

  45. Genomics of complex disorders I (2008) Genome Med 2(3–4) 303–330. https://doi.org/10.1007/s11568-009-9104-7

  46. Cuenca S, Ruiz-Cano MJ, Gimeno-Blanes JR, Jurado A, Salas C, Gomez-Diaz I, Padron-Barthe L, Grillo JJ, Vilches C, Segovia J, Pascual-Figal D, Lara-Pezzi E, Monserrat L, Alonso-Pulpon L, Garcia-Pavia P (2016) Genetic basis of familial dilated cardiomyopathy patients undergoing heart transplantation. Transplantation 35(5):625–635. https://doi.org/10.1016/j.healun.2015.12.014

    Article  Google Scholar 

  47. Lakdawala NK, Funke BH, Baxter S, Cirino AL, Roberts AE, Judge DP, Johnson N, Mendelsohn NJ, Morel C, Care M, Chung WK, Jones C, Psychogios A, Duffy E, Rehm HL, White E, Seidman JG, Seidman CE, Ho CY (2012) Genetic testing for dilated cardiomyopathy in clinical practice. J Cardiac Fail 18(4):296–303. https://doi.org/10.1016/j.cardfail.2012.01.013

    Article  Google Scholar 

  48. Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation C, MacArthur DG, Farrall M, Cook SA, Watkins H (2017) Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genetics Med 19(2):192–203. https://doi.org/10.1038/gim.2016.90

    Article  Google Scholar 

  49. Meng L, Pammi M, Saronwala A, Magoulas P, Ghazi AR, Vetrini F, Zhang J, He W, Dharmadhikari AV, Qu C, Ward P, Braxton A, Narayanan S, Ge X, Tokita MJ, Santiago-Sim T, Dai H, Chiang T, Smith H, Azamian MS, Robak L, Bostwick BL, Schaaf CP, Potocki L, Scaglia F, Bacino CA, Hanchard NA, Wangler MF, Scott D, Brown C, Hu J, Belmont JW, Burrage LC, Graham BH, Sutton VR, Craigen WJ, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Muzny DM, Miller MJ, Wang X, Leduc MS, Xiao R, Liu P, Shaw C, Walkiewicz M, Bi W, Xia F, Lee B, Eng CM, Yang Y, Lalani SR (2017) Use of exome sequencing for infants in intensive care units: ascertainment of severe single-gene disorders and effect on medical management. JAMA Pediatr 171(12):e173438. https://doi.org/10.1001/jamapediatrics.2017.3438

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This study was funded by the Natural Science Foundation of China (Grant Number: 81873498), the Natural Science Foundation of Shandong Province (Grant Number: ZR2019MH015), the Jinan Science and Technology Development Plan (Grant Number 201805020), and Special Expert of Taishan Scholars (Grant Number: TS201511099).

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Authors and Affiliations

  1. Department of Pediatrics, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, People’s Republic of China

    Yan Wang & Bo Han

  2. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, People’s Republic of China

    Yan Wang, Bo Han, Youfei Fan, Yingchun Yi, Jianli Lv, Jing Wang, Xiaofei Yang, Diandong Jiang, Lijian Zhao, Jianjun Zhang & Hui Yuan

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  1. Yan Wang
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Contributions

All authors contributed to study conception and design. YW and BH collected patient data and prepared the manuscript. YF, XY, JL, and JW contributed to the clinical evaluation of patients and revision of the manuscript. YY, HY, LZ, and JZ analyzed and interpreted the genetic data and surveyed the literature relevant to the mutations. All authors reviewed the results and approved the final version of the manuscript.

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Correspondence to Bo Han.

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All authors and study participants declare their unconditional consent toward publication of this manuscript and its associated data in a peer-reviewed journal.

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Our study received ethics approval (NSFC: NO.2018-115) from the ethics committee of Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University.

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Informed consent was obtained from the parents or carers of all participants included in the study.

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Wang, Y., Han, B., Fan, Y. et al. Next-Generation Sequencing Reveals Novel Genetic Variants for Dilated Cardiomyopathy in Pediatric Chinese Patients. Pediatr Cardiol 43, 110–120 (2022). https://doi.org/10.1007/s00246-021-02698-8

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