Cardiovascular Genetics

Cardiovascular Anesthesiology and Critical Care Laboratory

The Cardiovascular Anesthesiology and Critical Care laboratory is dedicated to understanding the complex physiology of critically ill children and to the development of monitoring tools to help bedside clinicians who are caring for the sickest pediatric patients.

Experiments are being conducted to explore the mechanisms behind the brain’s ability to regulate blood flow under conditions of traumatic brain injury, shock and cardiopulmonary bypass. Clinical research efforts in the detection and treatment of neurologic injuries acquired by children with critical heart disease are also underway.


John Welsh Cardiovascular Diagnostic Laboratory

The John Welsh Cardiovascular Diagnostic laboratory offers state-of-the-art molecular diagnostic testing for cardiovascular diseases and rapid molecular testing of heart tissue, lung tissue and other organ specimens and bodily fluids for viruses. These tests are focused specifically for viruses identified as causing heart disease in children and adults as well as in the fetus.

The laboratory also offers genetic testing for DNA mutations associated with cardiac disease. This close relationship between the research and the diagnostic laboratories allows us to identify novel disease-associated genes and mutations in the research laboratory and transfer this knowledge directly to the patient through the diagnostic laboratory, allowing “bench-to-beside” service.


Pediatric Cardiac Bioengineering Lab

Research in the Pediatric Cardiac Bioengineering laboratory focuses on the influences of biophysical cues such as stress, strain, shear, substrate stiffness and electrical stimulation on the development and maturation of heart cells and tissues.

The new Texas Children’s Hospital Pavilion for Women, opening fall 2011, affords a unique opportunity for multidisciplinary research collaboration between congenital heart surgery, fetal medicine and fetal surgery. Our physicians are working to develop heart tissue grown from stem cells taken from the amniotic fluid of patients’ mothers. This tissue will be genetically identical to the child and will grow with the patient.


Fetal Cardiology Research

The Fetal Cardiology team, which is a collaboration between the TCH Heart Center and TCH Fetal Center, is investigating novel fetal therapies for improving left heart growth in fetuses with small left-sided structures, including catheter-based interventions and a current trial investigating maternal oxygen as a therapy. For more information, please contact the Cardiovascular Clinical Research Core at 832-826-2064 or sandrea@texaschildrens.org


Aortic Disease Research

The Cardiovascular Genetics Clinic team is conducting research in patients with Marfan syndrome and related disorders to help determine how best to predict adverse events in young people with these disorders, and how best to improve outcomes.

Families with Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, Turner syndrome, bicuspid aortic valve with aortic dilation, familial thoracic aortic aneurysm and dissections, or carriers of genes causing any of the above may be eligible for one or more of our studies.  For more information, please contact the Cardiovascular Clinical Research Core at 832-826-2064 or sandrea@texaschildrens.org


Publications

Morris, SA. Arterial Tortuosity in Genetic Arteriopathies. Current Opinion in Cardiology 2015 Nov;30(6):587-93. PMID: 26398550

D'Alessandro LC, Al Turki S, Manickaraj AK, Manase D, Mulder BJ, Bergin L, Rosenberg HC, Mondal T, Gordon E, Lougheed J, Smythe J, Devriendt K, Bhattacharya S, Watkins H, Bentham J, Bowdin S, Hurles ME, Mital S. Exome sequencing identifies rare variants in multiple genes in atrioventricular septal defect. Genet Med. 2015 May 21. PMID: 25996639.

Frischhertz BP, Shamszad P, Pedroza C, Milewicz DM, Morris SA. Thoracic Aortic Dissection and Rupture in Congenital Heart Disease: A Population Based Study. International Journal of Cardiology. 2015 Mar 4;184:521-527. PMID 25767008

Prakash A, Adlakha H, Rabideau N, Hass CJ, Morris SA, Geva T, Gauvreau K, Singh MN, Lacro RV. Segmental Aortic Stiffness in Children and Young Adults with Connective Tissue Disorders: Relationships with Age, Aortic Size, Rate of Dilation and Surgical Root Replacement. Circulation. 2015;132:595-602. PMID: 26115544

Lopez KN, Marengo LK, Canfield MA, Belmont JW, Dickerson HA. Racial disparities in heterotaxy syndrome. Birth Defects Res A Clin Mol Teratol. 2015 Sep 2. doi: 10.1002/bdra.23416. [Epub ahead of print] PubMed PMID: 26333177.  

Manase D, D'Alessandro LC, Manickaraj AK, Al Turki S, Hurles ME, Mital S. High throughput exome coverage of clinically relevant cardiac genes. BMC Med Genomics. 2014 Dec 11;7:67. doi: 10.1186/s12920-014-0067-8. PubMed PMID: 25496018; PubMed Central PMCID: PMC4272796.  

Reinstein E, Morris SA, Rimoin DL, Robertson SP, Lacro RV. Arterial tortuosity in patients with Filamin A- associated vascular aneurysms. Am J Med Genet A. 2014 Nov;164A(11):2961-3. PMID: 25124759

Al Turki S, Manickaraj AK, Mercer CL, Gerety SS, Hitz MP, Lindsay S, D'Alessandro LC, Swaminathan GJ, Bentham J, Arndt AK, Low J, Breckpot J, Gewillig M, Thienpont B, Abdul-Khaliq H, Harnack C, Hoff K, Kramer HH, Schubert S, Siebert R, Toka O, Cosgrove C, Watkins H, Lucassen AM, O'Kelly IM, Salmon AP, Bu'lock FA, Granados-Riveron J, Setchfield K, Thornborough C, Brook JD, Mulder B, Klaassen S, Bhattacharya S, Devriendt K, Fitzpatrick DF; UK10K Consortium, Wilson DI, Mital S, Hurles ME. Rare variants in NR2F2 cause congenital heart defects in humans. Am J Hum Genet. 2014 Apr 3;94(4):574-85. doi: 10.1016/j.ajhg.2014.03.007. Erratum in: Am J Hum Genet. 2014 Jul 3;95(1):126. PubMed PMID: 24702954; PubMed Central PMCID: PMC3980509.

3: Lalani SR, Belmont JW. Genetic basis of congenital cardiovascular malformations. Eur J Med Genet. 2014 Aug;57(8):402-13. doi: 10.1016/j.ejmg.2014.04.010. Epub 2014 Apr 30. Review. PubMed PMID: 24793338; PubMed Central PMCID: PMC4152939.  

Lalani SR, Ware SM, Wang X, Zapata G, Tian Q, Franco LM, Jiang Z, Bucasas K, Scott DA, Campeau PM, Hanchard N, Umaña L, Cast A, Patel A, Cheung SW, McBride KL, Bray M, Craig Chinault A, Boggs BA, Huang M, Baker MR, Hamilton S, Towbin J,  Jefferies JL, Fernbach SD, Potocki L, Belmont JW. MCTP2 is a dosage-sensitive gene required for cardiac outflow tract development. Hum Mol Genet. 2013 Nov 1;22(21):4339-48. doi: 10.1093/hmg/ddt283. Epub 2013 Jun 16. PubMed PMID: 23773997; PubMed Central PMCID: PMC3792692.  

D'Alessandro LC, Werner P, Xie HM, Hakonarson H, White PS, Goldmuntz E. The prevalence of 16p12.1 microdeletion in patients with left-sided cardiac lesions.  Congenit Heart Dis. 2014 Jan-Feb;9(1):83-6. doi: 10.1111/chd.12097. Epub 2013 May 20. PubMed PMID: 23682798; PubMed Central PMCID: PMC4575124.  

Shamszad P, Barnes JN, Morris SA. Aortic Dissection in Hospitalized Children and Young Adults: A Multiinstitutional Study. Congenit Heart Dis. 2013 May 20. PMID: 23682693

Binesh Marvasti T, D'Alessandro LC, Manase D, Papaz T, Mital S. Personalized medicine in the care of the child with congenital heart disease: discovery to application. Congenit Heart Dis. 2013 May-Jun;8(3):266-9. doi: 10.1111/chd.12061. Epub 2013 Apr 22. PubMed PMID: 23601919.  

D'Alessandro LC, Casey B, Siu VM. Situs inversus totalis and a novel ZIC3 mutation in a family with X-linked heterotaxy. Congenit Heart Dis. 2013 Mar-Apr;8(2):E36-40. doi: 10.1111/j.1747-0803.2011.00602.x. Epub 2011 Dec 16. PubMed PMID: 22171628. 

D'Alessandro LC, Latney BC, Paluru PC, Goldmuntz E. The phenotypic spectrum of ZIC3 mutations includes isolated d-transposition of the great arteries and double outlet right ventricle. Am J Med Genet A. 2013 Apr;161A(4):792-802. doi: 10.1002/ajmg.a.35849. Epub 2013 Feb 20. PubMed PMID: 23427188; PubMed Central PMCID: PMC3707401.  

Lalani SR, Shaw C, Wang X, Patel A, Patterson LW, Kolodziejska K, Szafranski P, Ou Z, Tian Q, Kang SH, Jinnah A, Ali S, Malik A, Hixson P, Potocki L, Lupski JR, Stankiewicz P, Bacino CA, Dawson B, Beaudet AL, Boricha FM, Whittaker R, Li C, Ware SM, Cheung SW, Penny DJ, Jefferies JL, Belmont JW. Rare DNA copy number variants in cardiovascular malformations with extracardiac abnormalities. Eur J Hum Genet. 2013 Feb;21(2):173-81. doi: 10.1038/ejhg.2012.155. Epub 2012 Aug 29. PubMed PMID: 22929023; PubMed Central PMCID: PMC3548268.  

Lin KY, D'Alessandro LC, Goldmuntz E. Genetic testing in congenital heart disease: ethical considerations. World J Pediatr Congenit Heart Surg. 2013 Jan;4(1):53-7. doi: 10.1177/2150135112459523. PubMed PMID: 23799755.  

Morris SA, Orbach DB, Geva T, Singh MN, Gauvreau K, Lacro RV. Increased Vertebral Artery Tortuosity Index Is Associated With Adverse Outcomes in Children and Young Adults With Connective Tissue Disorders. Circulation. 2011 Jul 26;124(4):388-96. PMID: 21730308

Villanueva MP, Aiyer AR, Muller S, Pletcher MT, Liu X, Emanuel B, Srivastava D, Reeves RH. Genetic and comparative mapping of genes dysregulated in mouse hearts lacking the Hand2 transcription factor gene. Genomics 2002; 80(6):593-600. PMID: 12504851

Cody JD, Ghidoni PD, DuPont BR, Hale DE, Hilsenbeck SG, Stratton RF, Hoffman DS, Muller S, Schaub RL, Leach RJ, Kaye CI. Congenital Anomalies and Anthropometry of 42 Individuals with deletions of chromosome 18. American Journal of Medical Genetics 1999; 85(5):455-62. PMID: 104054