Assistant Professor, Department of Molecular and Human Genetics
Assistant Director, Cytogenetics Laboratory

M.D., Aga Khan University, Pakistan, 1994
Resident in Pediatrics, Hershey Medical Center, Hershey, PA, 1996
Fellow in Medical Genetics, Baylor College of Medicine, Houston, TX, 1999
Fellow in Clinical Cytogenetics, Baylor College of Medicine, Houston, TX, 2004

RESEARCH INTERESTS:

Genetic etiology of CHARGE syndrome: Our laboratory is interested in understanding the genetic etiology of CHARGE syndrome, a sporadic condition, known to occur in at least 1 in 10,000 births. Characteristic associated anomalies include ocular coloboma, choanal atresia, cranial nerve defects, distinctive external and inner ear abnormalities, hearing loss, cardiovascular malformations, urogenital anomalies, and growth retardation. Mutations in CHD7 gene, encoding the chromodomain helicase DNA binding protein, are known to be associated with CHARGE syndrome in about 2/3 cases. We have performed extensive genotype-phenotype analysis in a large number of individuals with this syndrome and determined important phenotypic differences between the mutation positive and negative groups. Our laboratory is interested in using advanced molecular cytogenetic tools to identify other genes underlying this condition, as about one-third of individuals with CHARGE syndrome have no known aberrations involving the CHD7 gene.

Using genomic microarrays to identify cytogenetic abnormalities in individuals with cardiovascular malformations (CVM): The cytogenetic abnormalities associated with heart defects have been an important tool in positional cloning of numerous genes involved in cardiac patterning. However, most of these abnormalities involve large genomic regions encompassing hundreds of genes and are difficult to explore. One strategy for investigating the etiology of CVM in the affected individuals is to use array-based comparative genomic hybridization (CGH) to identify submicroscopic regions with copy number alterations that could be effectively investigated with candidate gene sequencing in a large cohort of individuals with specific CVM. The targeted array-CGH, also known as chromosomal microarray analysis (CMA) is a molecular cytogenetic diagnostic test developed at the Kleberg Cytogenetics Laboratory at Baylor College of Medicine that has identified genomic copy number alterations in non-polymorphic loci in a number of individuals with CVM. Our laboratory is interested in using CMA as a diagnostic tool to identify candidate regions involved in cardiac patterning. The CMA has identified candidate genes underlying various CVM such as left ventricular outflow tract obstruction defects and Wolff-Parkinson-White syndrome (WPW). We have performed high-resolution genome-wide chromosomal copy number analysis in these individuals and are currently screening a large number of individuals with specific LVOTO defects and WPW for mutations in candidate genes identified through the targeted array-CGH.

SELECTED PUBLICATIONS:

1. Lalani SR, Belmont JW. CHARGE syndrome. In the Encyclopedia of Molecular Mechanisms of Disease. Springer Publishing House (eds.), in press.

2. Lalani SR, Hefner M, Belmont J, Davenport S (2006). CHARGE. In GeneReviews at GeneTests: Medical Genetics Information Resource [Database online]. Copyright, University of Washington, Seattle, 1997-2006. Available at http://www.genetests.org.

3. Sahoo T, Cheung SW, Ward P, Darilek S, Patel A, del Gaudio D, Kang SH, Lalani SR, Li J, McAdoo S, Burke A, Shaw CA, Stankiewicz P, Chinault AC, Van den Veyver IB, Roa BB, Beaudet AL, Eng CM (2006). Prenatal diagnosis of chromosomal abnormalities using array-based comparative genomic hybridization. Genet. Med. 8: 719-727.

4. Lalani SR, Safiullah AM, Fernbach SD, Harutyunyan KG, Thaller C, Peterson LE, McPherson JD, Gibbs RA, White LD, Hefner M, Davenport SLH, Graham Jr. 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. Hum. Genet. 78: 303-314.

5. Lalani SR, Sahoo T, Sanders ME, Peters SU, Bejjani BA (2006). Coarctation of the aorta and mild to moderate developmental delay in a child with a de novo deletion of chromosome 15(q21.1q22.2). BMC. Med. Genet. 7: 8.

6. Lalani SR, Vladutiu GD, Plunkett K, Lotze TE, Adesina AM, Scaglia F (2005). Isolated mitochondrial myopathy associated with muscle coenzyme Q10 deficiency. Arch. Neurol. 62: 317-320.

7. Lalani SR, Safiullah AM, Molinari LM, Fernbach SD, Martin DM, Belmont JW (2004). SEMA3E mutation in a patient with CHARGE syndrome. J. Med. Genet. 41: e94.

8. Lalani SR, Stockton DW, Bacino C, Molinari LM, Glass NL, Fernbach SD, Towbin JA, Craigen WJ, Graham JM, Jr., Hefner MA, Lin AE, McBride KL, Davenport SL, Belmont JW (2003). Toward a genetic etiology of CHARGE syndrome: I. A systematic scan for submicroscopic deletions. Am. J. Med. Genet. A 118: 260-266.

9. Edelmann L, Spiteri E, McCain N, Goldberg R, Pandita RK, Duong S, Fox J, Blumenthal D, Lalani SR, Shaffer LG, Morrow BE (1999). A common breakpoint on 11q23 in carriers of the constitutional t(11;22) translocation. Am. J. Hum. Genet. 65: 1608-1616.

For more publications, see listing on Pub Med.

CLINICAL INFORMATION:

Board Certifications:
American Board of Medical Genetics: Clinical Cytogenetics, Clinical Genetics
American Board of Pediatrics

Primary Focus: CHARGE syndrome; Use of array-comparative genomic hybridization in identifying molecular etiology of cardiovascular malformations.

Professional Organizations:
Member, American Society of Human Genetics
Member of Scientific Advisory Board, CHARGE Syndrome Foundation

CONTACT INFORMATION:

Seema R. Lalani, M.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, T828
Houston, Texas 77030, U.S.A.
Mail Stop: BCM225

Phone: 713-798-6550
Fax: 713-798-8142
E-mail:

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