B.A., University of Texas, 1974
M.D., Ph.D., Baylor College of Medicine, 1981
Resident in Pediatrics, Children's Hospital, National Medical Center, Washington, D.C., 1983
Resident in Pedriatrics, Baylor College of Medicine, 1984
Fellow in Medical Genetics, Baylor College of Medicine, 1986

Cardiovascular Genetics Clinic Website: www.cardiogene.org

RESEARCH INTERESTS:
Cardiovascular Genetics: Congenital heart defects occur in about seven per 1000 live births. We are analyzing several clinical disorders that provide specific routes to gene identification. One project focuses on the underlying basis for CHARGE Syndrome. CHARGE is a complex phenotype that involves the development of the eye, ear, cranial nerves, brain, genitourinary system, and heart. Recently a gene, CHD7, has been found to cause CHARGE in about 60% of patients. Using a large set of CHARGE cases we have characterized the mutational spectrum in CHD7. We are using microarray technology to screen for deletion alleles that may point to additional genetic loci involved in CHARGE.

The second class of disorders that we are studying is called heterotaxy. These conditions are caused by disturbance in the establishment of the left- right body axis. So far mutations in four genes have been identified as causing human heterotaxy using this sample set—ZIC3, ACVR2B, LEFTYA, and CFC1/cryptic. Current efforts focus on the NODAL-dependent signaling pathway that operates in the node and left lateral plate mesoderm. Future studies will extend this into the node-specific functional pathways and the establishment of the midline. We have also been studying a mouse knockout mutant in Zic3 as a model for human heterotaxy. Our goal is to place Zic3 into one or more the critical pathways that are required for left right asymmetry. These studies have revealed an unexpected role for Zic3 in gastrulation.

The lab is also studying the genetics of hypoplastic left heart, coarctation of the aorta, aortic stenosis, and bicuspid aortic valve. Together, these defects are called left ventricular outflow tract obstruction (LVOTO) defects. Linkage analysis has identified several promising loci. We are using microarray copy number analyses to identify cases with underlying gene copy number aberrations. This has led to the finding of many previously unrecognized chromosomal imbalances in these children.

Back to top

SELECTED PUBLICATIONS:
1. Lalani SR, Safiullah AM, Fernbach SD, Harutyunyan KG, Thaller C, Peterson LE, McPherson JD, Gibbs RA, White LD, Hefner M, Davenport SL, Graham JM, Bacino CA, Glass NL, Towbin JA, Craigen WJ, Neish SR, Lin AE, Belmont JW (2006). Spectrum of CHD7 Mutations in 110 Individuals with CHARGE Syndrome and Genotype-Phenotype Correlation. Am. J. Med. Genet. 78: 303-314.

2. McBride KL, Pignatelli R, Lewin M, Ho T, Fernbach S, Menesses A, Lam W, Leal SM, Kaplan N, Schliekelman P, Towbin JA, Belmont JW (2005). Inheritance analysis of congenital left ventricular outflow tract obstruction malformations: Segregation, multiplex relative risk, and heritability. Am. J. Med. Genet. A 134: 180-186.

3. Ware SM, Peng J, Zhu L, Fernbach S, Colicos S, Casey B, Towbin J, Belmont JW (2004). Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects. Am. J. Med. Genet. 74: 93-105.

4. Purandare SM, Ware SM, Kwan KM, Gebbia M, Bassi MT, Deng JM, Vogel H, Behringer RR, Belmont JW, Casey B (2002). A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice. Development 129: 2293-2302.

5. Kakkis ED, Muenzer J, Tiller GE, Waber L, Belmont J, Passage M, Izykowski B, Phillips J, Doroshow R, Walot I, Hoft R, Neufeld EF (2001). Enzyme-replacement therapy in mucopolysaccharidosis I. N. Engl. J. Med. 344: 182-188.

6. Kosaki K, Bassi MT, Kosaki R, Lewin M, Belmont J, Schauer G, Casey B (1999). Characterization and mutation analysis of human LEFTY-A and LEFTY-B, homologues of murine genes implicated in left-right axis development. Am. J. Hum. Genet. 64: 712-721.

7. Allen RC, Armitage RJ, Conley ME, Rosenblatt H, Jenkins N, Copeland NG, Bedell MA, Edelhoff S, Disteche CM, Simoneaux DK, Fanslow WC, Belmont JW, Spriggs MK (1993). CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome. Science 259: 990-993.

8. Allen RC, Zoghbi HY, Moseley A, Rosenblatt H, Belmont JW (1992). Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen receptor gene correlates with X chromosome inactivation. Am. J. Hum. Genet. 51: 1221-1239.

9. Belmont JW, Henkel-Tigges J, Chang SMW, Wager-Smith K, Kellems RE, Dick JE, Magli MC, Phillips RA, Bernstein A, Caskey CT (1986). Expression of human adenosine deaminase in murine hematopoietic progenitor cells following retroviral transfer. Nature 322: 385-387.

For more publications, see listing on Pub Med.

Back to top

CLINICAL INFORMATION:
Board Certifications:
Medical Genetics
Pediatrics
Subspecialty Biochemical Genetics

Primary Focus:
Inborn Errors of Metabolism, Cardiovascular Genetics

Professional Organizations:
Member, American Society of Human Genetics
Member, American Society of Hematology
Member, American Society for Clinical Investigation
Member, Society for Pediatric Research

Back to top

Telephone: 713-798-4634
Fax: 713-798-8142
E-mail:

Cardiovascular Genetics Clinic Website: www.cardiogene.org

Back to top

Last Modified: 8/2007