References
Aalberts JJ, van Tintelen JP, Meijboom LJ, Polko A, Jongbloed JD, van
der Wal H, Pals G, Osinga J, Timmermans J, de Backer J, Bakker MK, van
Veldhuisen DJ, Hofstra RM, Mulder BJ, van den Berg MP. Relation between
genotype and left-ventricular dilatation in patients with Marfan
syndrome. Gene. 2014 Jan 15;534(1):40-3. doi:
10.1016/j.gene.2013.10.033. Epub 2013 Oct 24.
Alcalde M, Campuzano O, Berne P, García-Pavía P, Doltra A, Arbelo E,
Sarquella-Brugada G, Iglesias A, Alonso-Pulpon L, Brugada J, Brugada R.
Stop-gain mutations in PKP2 are associated with a later age of onset of
arrhythmogenic right ventricular cardiomyopathy. PLoS One . 2014
Jun 26;9(6):e100560. doi: 10.1371/journal.pone.0100560. eCollection
2014.
Baudhuin LM, Kotzer KE, Lagerstedt SA. Increased frequency of FBN1
truncating and splicing variants in Marfan syndrome patients with aortic
events. Genet Med. 2015 Mar;17(3):177-87. doi: 10.1038/gim.2014.91. Epub
2014 Aug 7.
Bienengraeber M, Olson TM, Selivanov VA, Kathmann EC, O’Cochlain F, Gao
F, Karger AB, Ballew JD, Hodgson DM, Zingman LV, Pang YP, Alekseev AE,
Terzic A. ABCC9 mutations identified in human dilated cardiomyopathy
disrupt catalytic KATP channel gating. Nat Genet. 2004
Apr;36(4):382-7. doi: 10.1038/ng1329. Epub 2004 Mar 21.
Bjerregaard P. Diagnosis and management of short QT syndrome.Heart Rhythm. 2018 Aug;15(8):1261-1267. doi:
10.1016/j.hrthm.2018.02.034. Epub 2018 Mar 2.
Campuzano O, Sanchez-Molero O, Allegue C, Coll M, Mademont-Soler I,
Selga E, Ferrer-Costa C, Mates J, Iglesias A, Sarquella-Brugada G, Cesar
S, Brugada J, Castellà J, Medallo J, Brugada R. Post-mortem genetic
analysis in juvenile cases of sudden cardiac death. Forensic Sci
Int . 2014 Dec;245:30-7. doi: 10.1016/j.forsciint.2014.10.004. Epub 2014
Oct 14.
Campuzano O, Sarquella-Brugada G, Cesar S, Arbelo E, Brugada J, Brugada
R. Recent Advances in Short QT Syndrome. Front Cardiovasc Med.2018 Oct 29;5:149. doi: 10.3389/fcvm.2018.00149.
Cerrone M, Montnach J, Lin X, Zhao YT, Zhang M, Agullo-Pascual E,
Leo-Macias A, Alvarado FJ, Dolgalev I, Karathanos TV, Malkani K, Van
Opbergen CJM, van Bavel JJA, Yang HQ, Vasquez C, Tester D, Fowler S,
Liang F, Rothenberg E, Heguy A, Morley GE, Coetzee WA, Trayanova NA,
Ackerman MJ, van Veen TAB, Valdivia HH, Delmar M. Plakophilin-2 is
required for transcription of genes that control calcium cycling and
cardiac rhythm. Nat Commun . 2017 Jul 24;8(1):106. doi:
10.1038/s41467-017-00127-0.
Cerrone M, Remme CA, Tadros R, Bezzina CR, Delmar M. Beyond the One
Gene-One Disease Paradigm: Complex Genetics and Pleiotropy in
Inheritable Cardiac Disorders. Circulation . 2019 Aug
13;140(7):595-610. doi: 10.1161/CIRCULATIONAHA.118.035954. Epub 2019 Aug
12.
Chen K, Rao M, Guo G, Duru F, Chen L, Chen X, Song J, Hu S. Recessive
variants in plakophilin-2 contributes to early-onset arrhythmogenic
cardiomyopathy with severe heart failure. Europace . 2019 Jun
1;21(6):970-977. doi: 10.1093/europace/euz026.
El-Battrawy I, Besler J, Liebe V, Schimpf R, Tülümen E, Rudic B, Lang S,
Wolpert C, Zhou X, Akin I, Borggrefe M. Long-Term Follow-Up of Patients
With Short QT Syndrome: Clinical Profile and Outcome. J Am Heart
Assoc. 2018 Dec 4;7(23):e010073. doi: 10.1161/JAHA.118.010073.
Faivre L, Collod-Beroud G, Loeys BL, Child A, Binquet C, Gautier E,
Callewaert B, Arbustini E, Mayer K, Arslan-Kirchner M, Kiotsekoglou A,
Comeglio P, Marziliano N, Dietz HC, Halliday D, Beroud C, Bonithon-Kopp
C, Claustres M, Muti C, Plauchu H, Robinson PN, Adès LC, Biggin A,
Benetts B, Brett M, Holman KJ, De Backer J, Coucke P, Francke U, De
Paepe A, Jondeau G, Boileau C. Effect of mutation type and location on
clinical outcome in 1,013 probands with Marfan syndrome or related
phenotypes and FBN1 mutations: an international study. Am J Hum Genet.
2007 Sep;81(3):454-66. doi: 10.1086/520125. Epub 2007 Jul 25.
Forleo C, D’Erchia AM, Sorrentino S, Manzari C, Chiara M, Iacoviello M,
Guaricci AI, De Santis D, Musci RL, La Spada A, Marangelli V, Pesole G,
Favale S. Targeted next-generation sequencing detects novel
gene-phenotype associations and expands the mutational spectrum in
cardiomyopathies. PLoS One . 2017 Jul 27;12(7):e0181842. doi:
10.1371/journal.pone.0181842. eCollection 2017.
Fressart V, Duthoit G, Donal E, Probst V, Deharo JC, Chevalier P, Klug
D, Dubourg O, Delacretaz E, Cosnay P, Scanu P, Extramiana F, Keller D,
Hidden-Lucet F, Simon F, Bessirard V, Roux-Buisson N, Hebert JL, Azarine
A, Casset-Senon D, Rouzet F, Lecarpentier Y, Fontaine G, Coirault C,
Frank R, Hainque B, Charron P.Desmosomal gene analysis in arrhythmogenic
right ventricular dysplasia/cardiomyopathy: spectrum of mutations and
clinical impact in practice. Europace . 2010 Jun;12(6):861-8. doi:
10.1093/europace/euq104. Epub 2010 Apr 16.
Gray B, Behr ER. New Insights Into the Genetic Basis of Inherited
Arrhythmia Syndromes. Circ Cardiovasc Genet . 2016
Dec;9(6):569-577. doi: 10.1161/CIRCGENETICS.116.001571.
Hu D, Barajas-Martínez H, Terzic A, Park S, Pfeiffer R, Burashnikov E,
Wu Y, Borggrefe M, Veltmann C, Schimpf R, Cai JJ, Nam GB, Deshmukh P,
Scheinman M, Preminger M, Steinberg J, López-Izquierdo A, Ponce-Balbuena
D, Wolpert C, Haïssaguerre M, Sánchez-Chapula JA, Antzelevitch C. ABCC9
is a novel Brugada and early repolarization syndrome susceptibility
gene. Int J Cardiol . 2014 Feb 15; 171(3): 431-42. doi:
10.1016/j.ijcard.2013.12.084. Epub 2014 Jan 4.
Jensen SA, Aspinall G, Handford PA. C-terminal propeptide is required
for fibrillin-1 secretion and blocks premature assembly through linkage
to domains cbEGF41-43. Proc Natl Acad Sci U S A. 2014 Jul
15;111(28):10155-60. doi: 10.1073/pnas.1401697111. Epub 2014 Jun 30.
Jo H, Koh G. Faster single-end alignment generation utilizing
multi-thread for BWA. Biomed Mater Eng . 2015;26 Suppl
1:S1791-1796.
Li Mura IE, Bauce B, Nava A, Fanciulli M, Vazza G, Mazzotti E, Rigato I,
De Bortoli M, Beffagna G, Lorenzon A, Calore M, Dazzo E, Nobile C,
Mostacciuolo ML, Corrado D, Basso C, Daliento L, Thiene G, Rampazzo A.
Identification of a PKP2 gene deletion in a family with arrhythmogenic
right ventricular cardiomyopathy. Eur J Hum Genet. 2013
Nov;21(11):1226-31. doi: 10.1038/ejhg.2013.39. Epub 2013 Mar 13.
Mogensen J, Murphy RT, Shaw T, Bahl A, Redwood C, Watkins H, Burke M,
Elliott PM, McKenna WJ. Severe disease expression of cardiac troponin C
and T mutations in patients with idiopathic dilated cardiomyopathy.J Am Coll Cardiol. 2004 Nov 16;44(10):2033-40. doi:
10.1016/j.jacc.2004.08.027.
Olde Nordkamp LR, Postema PG, Knops RE, van Dijk N, Limpens J, Wilde AA,
de Groot JR. Implantable cardioverter-defibrillator harm in young
patients with inherited arrhythmia syndromes: A systematic review and
meta-analysis of inappropriate shocks and complications. Heart
Rhythm . 2016 Feb;13(2):443-54. doi: 10.1016/j.hrthm.2015.09.010. Epub
2015 Sep 15.
Otten E, Lekanne Dit Deprez RH, Weiss MM, van Slegtenhorst M, Joosten M,
van der Smagt JJ, de Jonge N, Kerstjens-Frederikse WS, Roofthooft MT,
Balk AH, van den Berg MP, Ruiter JS, van Tintelen JP. Recurrent and
founder mutations in the Netherlands: mutation p.K217del in troponin T2,
causing dilated cardiomyopathy. Neth Heart J. 2010
Oct;18(10):478-85. doi: 10.1007/BF03091819.
Philips B, Madhavan S, James CA, te Riele AS, Murray B, Tichnell C,
Bhonsale A, Nazarian S, Judge DP, Calkins H, Tandri H, Cheng A.
Arrhythmogenic right ventricular dysplasia/cardiomyopathy and cardiac
sarcoidosis: distinguishing features when the diagnosis is unclear.Circ Arrhythm Electrophysiol . 2014 Apr;7(2):230-6. doi:
10.1161/CIRCEP.113.000932. Epub 2014 Mar 1.
Ramond F, Janin A, Di Filippo S, Chanavat V, Chalabreysse L,
Roux-Buisson N, Sanlaville D, Touraine R, Millat G. Homozygous PKP2
deletion associated with neonatal left ventricle noncompaction.Clin Genet. 2017 Jan;91(1):126-130. doi: 10.1111/cge.12780. Epub
2016 Apr 26.
Robinson P, Mirza M, Knott A, Abdulrazzak H, Willott R, Marston S,
Watkins H, Redwood C. Alterations in thin filament regulation induced by
a human cardiac troponin T mutant that causes dilated cardiomyopathy are
distinct from those induced by troponin T mutants that cause
hypertrophic cardiomyopathy. J Biol Chem . 2002 Oct
25;277(43):40710-6. doi: 10.1074/jbc.M203446200. Epub 2002 Aug 18.
Sakai LY, Keene DR, Renard M, De Backer J. FBN1: The disease-causing
gene for Marfan syndrome and other genetic disorders. Gene. 2016 Oct
10;591(1):279-291. doi: 10.1016/j.gene.2016.07.033. Epub 2016 Jul 18.
Sarquella-Brugada G, Campuzano O, Arbelo E, Brugada J, Brugada R.
Brugada syndrome: clinical and genetic findings. Genet Med. 2016
Jan;18(1):3-12. doi: 10.1038/gim.2015.35. Epub 2015 Apr 23.
Sieira J, Brugada P.The definition of the Brugada syndrome. Eur
Heart J. 2017 Oct 21;38(40):3029-3034. doi: 10.1093/eurheartj/ehx490.
Sieira J, Dendramis G, Brugada P. Pathogenesis and management of Brugada
syndrome. Nat Rev Cardiol. 2016 Dec;13(12):744-756. doi:
10.1038/nrcardio.2016.143. Epub 2016 Sep 15.
Singer ES, Ross SB, Skinner JR, Weintraub RG, Ingles J, Semsarian C,
Bagnall RD. Characterization of clinically relevant copy-number variants
from exomes of patients with inherited heart disease and unexplained
sudden cardiac death. Genet Med . 2021 Jan;23(1):86-93. doi:
10.1038/s41436-020-00970-5. Epub 2020 Sep 25.
Sonoda K, Ohno S, Otuki S, Kato K, Yagihara N, Watanabe H, Makiyama T,
Minamino T, Horie M. Quantitative analysis of PKP2 and neighbouring
genes in a patient with arrhythmogenic right ventricular cardiomyopathy
caused by heterozygous PKP2 deletion. Europace . 2017 Apr
1;19(4):644-650. doi: 10.1093/europace/euw038.
Tisma-Dupanovic S, Wagner JB, Shah S, Huang DT, Moss AJ. An adolescent
with possible arrhythmogenic right ventricular dysplasia and long QT
syndrome: evaluation and management. Ann Noninvasive
Electrocardiol . 2013 Jan;18(1):75-8. doi: 10.1111/anec.12043.
Van der Auwera GA, Carneiro MO, Hartl C, Poplin R, Del Angel G,
Levy-Moonshine A, Jordan T, Shakir K, Roazen D, Thibault J, Banks E,
Garimella KV, Altshuler D, Gabriel S, DePristo MA. From FastQ data to
high confidence variant calls: the Genome Analysis Toolkit best
practices pipeline. Curr Protoc Bioinformatics .
2013;43(1110):11.10.1-11.10.33. doi: 10.1002/0471250953.bi1110s43.
Xie S, Lan Z, Qu N, Wei X, Yu P, Zhu Q, Yang G, Wang J, Shi Q, Wang W,
Yang L, Yi X. Detection of truncated dystrophin lacking the C-terminal
domain in a Chinese pedigree by next-generation sequencing. Gene .
2012 May 10;499(1):139-42. doi: 10.1016/j.gene.2012.03.029. Epub 2012
Mar 9.
Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A,
Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS,
Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet
AL, Gibbs RA, Eng CM. Clinical whole-exome sequencing for the diagnosis
of mendelian disorders.
N Engl J Med . 2013 Oct 17;369(16):1502-11. doi:
10.1056/NEJMoa1306555. Epub 2013 Oct 2.
Zeng Y, Li J, Li G, Huang S, Yu W, Zhang Y, Chen D, Chen J, Liu J, Huang
X. Correction of the Marfan Syndrome Pathogenic FBN1 Mutation by Base
Editing in Human Cells and Heterozygous Embryos. Mol Ther. 2018 Nov
7;26(11):2631-2637. doi: 10.1016/j.ymthe.2018.08.007. Epub 2018 Aug 14.
Figure legendsFigure 1. Sanger sequencing analysis of six mutations in
patients with inherited heart diseases. A. The heterozygous mutation
(c.148_151delACAG) was identified in patient R42. B. The heterozygous
mutation (c.3589C>T) was identified in patient R44. C. The
heterozygous mutation (c.1237C>T) was identified in patient
R46. D. The heterozygous mutation (c.8286_8289delCATC) was identified
in patient R47. E. The heterozygous mutation (c.2490-6T>C)
was identified in patient R51. F. The heterozygous mutation
(c.650_652delAGA) was identified in patient R52.Figure 2. (A) There is a heterozygous mutation
c.3589C>T (p.Arg1197Cys) in ABCC9 gene located on
the 12: 21981972 chromosome in patient R44.(B) There is a heterozygous mutation c.8286_8289del
(p.Ile2763Leufs*15) in FBN1 gene located on the 15:48703514
chromosome in patient R47.(C) There is a heterozygous mutation c.148_151del
(p.Thr50Serfs*61) in PKP2 gene located on the 12:33049515
chromosome in patient R42, a heterozygous mutation
c.1237C>T (p.Arg413Ter) in PKP2 gene located on the
12:33003841 chromosome in patient R46, and a heterozygous mutation
c.2490-6T>C in PKP2 gene located on the 12:32945671
chromosome in patient R51.(D) There is a heterozygous mutation c.650_652delAGA
(p.Lys217del) in TNNT2 gene located on the 1:201331099 chromosome
in patient 52.Table 1. Genetic and clinical profile of each inherited heart
disease patient carrying potentially pathogenic variants.