Expanding the phenotype of Timothy syndrome type 2: An adolescent with ventricular fibrillation but normal development

American Journal of Medical Genetics, Part A

Volumn 167, Issue 3, 2015, Pages 629-634

  Hiippala, Anita ^a   Tallila, Jonna ^b   Myllykangas, Samuel ^b,c   Koskenvuo, Juha W ^a,b   Alastalo, Tero Pekka ^a,b  

^a UNIVERSITY OF HELSINKI   (Finland)

^b Blueprint Genetics ^*  (Finland)

^c UNIVERSITY OF HELSINKI   (Finland)

Author keywords

CACNA1C; Channelopathies; Genetics; Idiopathic ventricular fibrillation; Long QT syndrome; OS Seq; Timothy syndrome

Indexed keywords

AMINO ACID; DNA; GLYCINE; SERINE; ALPHA CATENIN; CACNA1C PROTEIN, HUMAN; CALCIUM CHANNEL L TYPE; CTNNA3 PROTEIN, HUMAN; PKP2 PROTEIN, HUMAN; PLAKOPHILIN;

ADOLESCENT; AMINO ACID SUBSTITUTION; ARTICLE; BLOOD ANALYSIS; CACNA1C GENE; CASE REPORT; CHANNELOPATHY; DNA SEQUENCE; EXON; FEMALE; GENE; HEART VENTRICLE FIBRILLATION; HUMAN; IMPLANTABLE CARDIOVERTER DEFIBRILLATOR; MULTIPLE ORGAN FAILURE; MUTATIONAL ANALYSIS; NUCLEOTIDE SEQUENCE; PHENOTYPE; PROTEIN EXPRESSION; QT PROLONGATION; RESUSCITATION; SALIVA ANALYSIS; TIMOTHY SYNDROME TYPE 2; AUTISTIC DISORDER; ELECTROCARDIOGRAPHY; GENETIC ASSOCIATION STUDY; GENETICS; GENOME-WIDE ASSOCIATION STUDY; HIGH THROUGHPUT SEQUENCING; LONG QT SYNDROME; MUTATION; SYNDACTYLY; VENTRICULAR FIBRILLATION;

PHLEUM PRATENSE;

ADOLESCENT; ALPHA CATENIN; AUTISTIC DISORDER; CALCIUM CHANNELS, L-TYPE; ELECTROCARDIOGRAPHY; FEMALE; GENETIC ASSOCIATION STUDIES; GENOME-WIDE ASSOCIATION STUDY; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; LONG QT SYNDROME; MUTATION; PHENOTYPE; PLAKOPHILINS; SYNDACTYLY; VENTRICULAR FIBRILLATION;

EID: 84922985339     PISSN: 15524825     EISSN: 15524833     Source Type: Journal    
DOI: 10.1002/ajmg.a.36924     Document Type: Article

References (18)

1. Boczek NJ, Best JM, Tester DJ, Giudicessi JR, Middha S, Evans JM, Kamp TJ, Ackerman MJ. 2013. Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long QT syndrome. Circ Cardiovasc Genet 6:279-289.
2. Cohen-Kutner M, Yahalom Y, Trus M, Atlas D. 2012. Calcineurin Controls Voltage-Dependent-Inactivation (VDI) of the Normal and Timothy Cardiac Channels. Sci Rep 2:366.
3. Crotti L, Monti MC, Insolia R, Peljto A, Goosen A, Brink PA, Greenberg DA, Schwartz PJ, George AL. 2009. NOS1AP is a genetic modifier of the long-QT syndrome. Circulation 120:1657-1663.
4. Drum BML, Dixon RE, Yuan C, Cheng EP, Santana LF. 2014. Cellular mechanisms of ventricular arrhythmias in a mouse model of Timothy syndrome (long QT syndrome 8). J Mol Cell Card 66:63-71.
5. Duchatelet S, Crotti L, Peat RA, Denjoy I, Itoh H, Berthet M, Ohno S, Fressart V, Monti MC, Crocamo C, Pedrazzini M, Dagradi F, Vicentini A, Klug D, Brink PA, Goosen A, Swan H, Toivonen L, Lahtinen AM, Kontula K, Shimizu W, Horie M, George AL, Trégouët D-A, Guicheney P, Schwartz PJ. 2013. Identification of a KCNQ1 polymorphism acting as a protective modifier against arrhythmic risk in long-QT syndrome. Circ Cardiovasc Genet 6:354-361.
6. Endler G, Greinix H, Winkler K, Mitterbauer G, Mannhalter C. 1999. Genetic fingerprinting in mouthwashes of patients after allogeneic bone marrow transplantation. Bone Marrow Transplant 24:95-98.
7. Etheridge SP, Bowles NE, Arrington CB, Pilcher T, Rope A, Wilde AAM, Alders M, Saarel EV, Tavernier R, Timothy KW, Tristani-Firouzi M. 2011. Somatic mosaicism contributes to phenotypic variation in Timothy syndrome. Am J Med Genet 155A: 1:2578-2583.
8. Gillis J, Burashnikov E, Antzelevitch C, Blaser S, Gross G, Turner L, Babul-Hirji R, Chitayat D. 2012. Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome. Am J Med Genet 158A:182-187.
9. Hofmann F, Flockerzi V, Kahl S, Wegener JW. 2014. L-Type CaV1.2 Calcium Channels: From In Vitro Findings to In Vivo Function. Physiol Rev 94:303-326.
10. Kaab S, Crawford DC, Sinner MF, Behr ER, Kannankeril PJ, Wilde AAM, Bezzina CR, Schulze-Bahr E, Guicheney P, Bishopric NH, Myerburg RJ, Schott JJ, Pfeufer A, Beckmann BM, Martens E, Zhang T, Stallmeyer B, Zumhagen S, Denjoy I, Bardai A, Van Gelder IC, Jamshidi Y, Dalageorgou C, Marshall V, Jeffery S, Shakir S, Camm AJ, Steinbeck G, Perz S, Lichtner P, Meitinger T, Peters A, Wichmann HE, Ingram C, Bradford Y, Carter S, Norris K, Ritchie MD, George AL, Roden DM. 2012. A Large Candidate Gene Survey Identifies the KCNE1 D85N Polymorphism as a Possible Modulator of Drug-Induced Torsades de Pointes. Circ Cardiovasc Genet 5:91-99.
11. Marks ML, Whisler SL, Clericuzio C, Keating M. 1995. A new form of long QT syndrome associated with syndactyly. J Am Coll Cardiol 25:59-64.
12. Myllykangas S, Buenrostro JD, Natsoulis G, Bell JM, Ji HP. 2011. Efficient targeted resequencing of human germline and cancer genomes by oligonucleotide-selective sequencing. Nature Biotechnol 29:1024-1027.
13. Pfeufer A, Sanna S, Arking DE, Müller M, Gateva V, Fuchsberger C, Ehret GB, Orrú M, Pattaro C, Köttgen A, Perz S, Usala G, Barbalic M, Li M, Pütz B, Scuteri A, Prineas RJ, Sinner MF, Gieger C, Najjar SS, Kao WHL, Mühleisen TW, Dei M, Happle C, Möhlenkamp S, Crisponi L, Erbel R, Jöckel K-H, Naitza S, Steinbeck G, Marroni F, Hicks AA, Lakatta E, Müller-Myhsok B, Pramstaller PP, Wichmann H-E, Schlessinger D, Boerwinkle E, Meitinger T, Uda M, Coresh J, Kääb S, Abecasis GR, Chakravarti A. 2009. Common variants at ten loci modulate the QT interval duration in the QTSCD Study. Nature Genet 41:407-414.
14. Reichenbach H, Meister EM, Theile H. 1992. The heart-hand syndrome. A new variant of disorders of heart conduction and syndactylia including osseous changes in hands and feet. Kinderarztl Prax 60:54-56.
15. Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C, Schwartz PJ, Joseph RM, Condouris K, Tager-Flusberg H, Priori SG, Sanguinetti MC, Keating MT. 2004. Ca(V) 1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119:19-31.
16. Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, Sanguinetti MC, Keating MT. 2005. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci USA 102:8089-8096.
17. Thiede C, Prange-Krex G, Freiberg-Richter J, Bornhäuser M, Ehninger G. 2000. Buccal swabs but not mouthwash samples can be used to obtain pretransplant DNA fingerprints from recipients of allogeneic bone marrow transplants. Bone Marrow Transplant 25:575-577.
18. Tomás M, Napolitano C, De Giuli L, Bloise R, Subirana I, Malovini A, Bellazzi R, Arking DE, Marban E, Chakravarti A, Spooner PM, Priori SG. 2010. Polymorphisms in the NOS1AP gene modulate QT interval duration and risk of arrhythmias in the long QT syndrome. J Am Coll Cardiol 55:2745-2752.