Seema R. Lalani, M.D.
Assistant Professor of Molecular and Human Genetics
Assistant Director, Cytogenetics Laboratory, BCM Medical Genetics Laboratories
M.D., Aga Khan University, Pakistan, 1994
Resident, Pediatrics, Hershey Medical Center, 1996
Fellow, Medical Genetics, Baylor College of Medicine, 1999
Fellow, Clinical Cytogenetics, Baylor College of Medicine, 2004
American Board of Medical Genetics: Clinical Cytogenetics
American Board of Medical Genetics: Clinical Genetics
American Board of Pediatrics
Member, American Society of Human Genetics
Member, Society of Pediatric Research
CHARGE syndrome; clinical use of array-comparative genomic hybridization studies in birth defects including cardiovascular malformations.
I am interested in the application of molecular cytogenetic diagnostic tools such as array-comparative genomic hybridization (CGH), also known as chromosomal microarray analysis (CMA) in understanding the genetic basis of birth defects. Our laboratory is specifically interested in using CMA as a tool to identify candidate regions involved in cardiac patterning. Clinically significant CVMs occur in 5-8 per 1000 live births, yet, the cause of these malformations is unknown in the majority of cases. Recurrent copy number variations are among the known causes of syndromic CVMs, accounting for an important fraction of cases. Our strategy has been to use array-CGH to identify genomic regions with copy number alterations that could be effectively investigated with candidate gene sequencing in a large cohort of individuals with specific CVM. Using this tool, we have identified genes underlying left ventricular outflow tract obstruction defects and Wolff-Parkinson-White syndrome (WPW). We have performed high-resolution genome-wide DNA copy number analyses in over 700 individuals with CVM and have identified novel loci that are involved in CVM. We have recruited over 150 families with Wolff-Parkinson-White syndrome and are interested in understanding the genetic basis of this pre-excitation syndrome that affects 1-3/1000 individuals.
We are also interested in studying low-frequency population-specific copy number variations linked to certain traits such as early language delay and autism spectrum disorders. We have recently identified a 4-kb deletion, removing exon 3 of TM4SF20, which co-segregates with cerebral white matter hyperintensities and early childhood language delay in multiple families, predominantly from Southeast Asia. This deletion which has an allele frequency of about 1% in the Vietnamese Kinh population, is embedded in a common ancestral haplotype. We are currently recruiting multiple families of Vietnamese, Thai, Burmese, Filipino, Indonesian, and Micronesian descent to understand the global impact of this low-frequency, highly penetrant allele on communication disorders and premature brain aging in this population.
- 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 (2013). MCTP2 is a dosage-sensitive gene required for cardiac outflow tract development. Hum. Mol. Genet., in press. PubMed PMID: 23773997
- Wiszniewski W, Hunter JV, Hanchard NA, Willer JR, Shaw C, Tian Q, Illner A, Wang X, (.....), Lalani SR (2013). TM4SF20 Ancestral Deletion and Susceptibility to a Pediatric Disorder of Early Language Delay and Cerebral White Matter Hyperintensities. Am. J. Hum. Genet. 93(2): 197-210. PubMed PMID: 23810381
- 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 (2013). Rare DNA Copy Number Variants in Cardiovascular Malformations with Extracardiac abnormalities. Eur. J. Med. Genet. 21(2): 173-81. PubMed PMID: 22929023
- Liu P, Erez A, Nagamani SC, Dhar SU, Kołodziejska KE, Dharmadhikari AV, Cooper ML, Wiszniewska J, Zhang F, Withers MA, Bacino CA, Campos-Acevedo LD, Delgado MR, Freedenberg D, Garnica A, Grebe TA, Hernández-Almaguer D, Immken L, Lalani SR, McLean SD, Northrup H, Scaglia F, Strathearn L, Trapane P, Kang SH, Patel A, Cheung SW, Hastings PJ, Stankiewicz P, Lupski JR, Bi W (2011). Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. Cell 146(6): 889-903. PubMed PMID: 21925314
- Layman WS, McEwen DP, Beyer LA, Lalani SR, Fernbach SD, Oh E, Swaroop A, Hegg CC, Raphael Y, Martens JR, Martin DM (2009). Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome. Hum. Mol. Genet. 18(11): 1909-23. PubMed PMID: 19279158
- Lalani SR, Thakuria JV, Cox GF, Wang X, Bi W, Bray MS, Shaw C, Cheung SW, Chinault AC, Boggs BA, Ou Z, Brundage EK, Lupski JR, Gentile J, Waisbren S, Pursley A, Ma L, Khajavi M, Zapata G, Friedman R, Kim JJ, Towbin JA, Stankiewicz P, Schnittger S, Hansmann I, Ai T, Sood S, Wehrens XH, Martin JF, Belmont JW, Potocki L (2009). 20p12.3 microdeletion predisposes to Wolff-Parkinson-White syndrome with variable neurocognitive deficits. J. Med. Genet. 46(3): 168-75. PubMed PMID: 18812404
- Brunetti-Pierri N, Berg JS, Scaglia F, Belmont J, Bacino CA, Sahoo T, Lalani SR, Graham B, Lee B, Shinawi M, Shen J, Kang SH, Pursley A, Lotze T, Kennedy G, Lansky-Shafer S, Weaver C, Roeder ER, Grebe TA, Arnold GL, Hutchison T, Reimschisel T, Amato S, Geragthy MT, Innis JW, Obersztyn E, Nowakowska B, Rosengren SS, Bader PI, Grange DK, Naqvi S, Garnica AD, Bernes SM, Fong CT, Summers A, Walters WD, Lupski JR, Stankiewicz P, Cheung SW, Patel A (2008). Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nat. Genet. 40(12): 1466-71. PubMed PMID: 19029900
- Lalani SR, Belmont JW (2009). CHARGE syndrome. In Lang, F (Ed.) Encyclopedia of Molecular Mechanisms of Disease. Springer Publishing House.
- 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. PubMed PMID: 20301296
- 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(2): 303-14. PubMed PMID: 16400610
Seema R. Lalani, M.D.
Children's Nutrition Research Center
1100 Bates St., CNRC-8005
Houston, TX, 77030, U.S.A.