- Obstetrics and Gynecology
- Maternal Fetal Medicine
- Baylor College of Medicine
- Houston, TX, US
- Dan L Duncan Comprehensive Cancer Center
- Baylor College of Medicine
- Houston, Texas, United States
- Fellowship at Baylor College Of Medicine
- Maternal-Fetal Medicine
- MD from University of Antwerp
- Residency at University Of Antwerp affiliated hospitals
- Obstetrics and Gynecology
- Clinical Fellowship at Baylor College Of Medicine
- Genetics and epigenetics of reproductive disorders; Aicardi syndrome; prenatal gene-environment interactions; prenatal genetics
My lab performs research to find the cause of Aicardi syndrome (AIC) a severe X-linked disorder that only affects girls. Children with AIC have developmental defects of eyes and brain, severe seizures and mental retardation. We are performing high-throughput sequencing studies to search for the mutation that causes AIC and detailed clinical phenotyping in collaboration with other investigators at BCM (Dr. V. Reid Sutton and Dr. Richard A. Lewis).
In our second project, we study complete hydatidiform moles (CHM), an abnormal development of the human placenta. Most CHM are diploid androgenetic (AnCHM) with a paternally inherited genome, suggesting that imbalance of imprinted gene expression causes CHM. Our research focuses on the cause of rare recurrent HMs that have a biparentally inherited diploid genome (BiHM) but show generalized defects of imprinting.
Mutations in NLRP7 or KHDC3L have been found in women with BiHM pregnancies. We use mice and embryonic stem cell culture models to characterize the function of NLRP7 and its homolog Nlrp2 in reprogramming of imprinting.
In the third project, we investigate in mice the mechanisms by which maternal diet or an adverse prenatal environment affect disease risk in offspring. We found that maternal low protein diet alters muscle growth and expression of cohesins in liver of offspring and are following up on this observation. We are also studying in genetic mouse models for autism whether adverse prenatal exposures, such as inflammation, stress and certain medications (such as oxytocin and antidepressants) worsen the phenotype in offspring and by which mechanisms.
We also study Goltz Syndrome or Focal Dermal Hypoplasia (FDH) an X-linked disorder characterized by variable defects of skin and appendages, skeletal defects, primarily of hands, feet and long bones, as well as other anomalies such as omphalocele and urogenital defects. We found that this disorder is caused by mutations in the PORCN gene in Xp11.23 and have now generated a mouse model with a conditional null mutation in Porcn that we are characterizing. PORCN encodes the human homolog of Drosophila porcupine which is essential for secretion of Wnt and Wnt signaling.
Finally, I am also interested in the clinical application of new cytogenomic technologies for prenatal diagnosis and their role in non-invasive methods for prenatal diagnosis of fetal genetic disorders.
- Wang X, Sutton VR, Eble TN, Lewis RA, Gunaratne P, Patel A, Van den Veyver IB. "A genome-wide screen for copy number alterations in Aicardi syndrome." Am J Med Genet A. 2009 October;149(10):2113-21. Pubmed PMID: 19760649
- Kou YC, Shao L, Peng HH, Rosetta R, del Gaudio D, Wagner AF, Al-Hussaini TK, Van den Veyver IB. "A recurrent intragenic genomic duplication, other novel mutations in NLRP7 and imprinting defects in recurrent biparental hydatidiform moles.." Mol. Hum. Reprod.. 2008 January;14(1):33-40. Pubmed PMID: 18039680
- Balasa A, Sanchez-Valle A, Sadikovic B, Sangi-Haghpeykar H, Bravo J, Chen L, Liu W, Wen S, Fiorotto ML, Van den Veyver IB. "Chronic maternal protein deprivation in mice is associated with overexpression of the cohesin-mediator complex in liver of their offspring." J Nutr. 2011 December;141(12):2106-12. Pubmed PMID: 22013202
- Liu W, Shaver TM, Balasa A, Ljungberg MC, Wang X, Wen S, Nguyen H, Van den Veyver IB. "Deletion of Porcn in mice leads to multiple developmental defects and models human focal dermal hypoplasia (Goltz syndrome)." PLoS ONE. 2012;7(3):e32331. Pubmed PMID: 22412863
- Sutton VR, Hopkins BJ, Eble TN, Gambhir N, Lewis RA, Van den Veyver IB. "Facial and physical features of Aicardi syndrome: infants to teenagers.." Am. J. Med. Genet. A. 2005 October 15;138(3):254-8. Pubmed PMID: 16158440
- Moglabey YB, Kircheisen R, Seoud M, El Mogharbel N, Van den Veyver I, Slim R. "Genetic mapping of a maternal locus responsible for familial hydatidiform moles.." Hum. Mol. Genet.. 1999 April;8(4):667-71. Pubmed PMID: 10072436
- Van den Veyver IB. "Microphthalmia with linear skin defects (MLS), Aicardi, and Goltz syndromes: are they related X-linked dominant male-lethal disorders?." Cytogenet. Genome Res.. 2002;99(41278):289-96. Pubmed PMID: 12900577
- Wang X, Reid Sutton V, Omar Peraza-Llanes J, Yu Z, Rosetta R, Kou YC, Eble TN, Patel A, Thaller C, Fang P, Van den Veyver IB. "Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia." Nat Genet. 2007 July;39(7):836-8. Pubmed PMID: 17546030
- Hopkins B, Sutton VR, Lewis RA, Van den Veyver I, Clark G. "Neuroimaging aspects of Aicardi syndrome.." Am. J. Med. Genet. A. 2008 November 15;146(22):2871-8. Pubmed PMID: 18925666
- Mahadevan S, Wen S, Wan Y-W, Peng H-H, Otta S, Liu Z, Iacovino M, Mahen EM, Kyba M, Sadikovic B, Van den Veyver IB. "NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters CpG methylation." Hum Mol Genet. 2014;23(3):706-16. Pubmed PMID: 24105472
- Mahadevan SK, Wen S, Balasa A, Fruhman G, Mateus J, Wagner A, Al-Hussaini T, Van den Veyver IB. "No evidence for mutations in NLRP7 and KHDC3L in women with androgenetic hydatidiform moles." Prenat Diagn. 2013;33(13):1242-7. Pubmed PMID: 24105752
- Eble TN, Sutton VR, Sangi-Haghpeykar H, Wang X, Jin W, Lewis RA, Fang P, Van den Veyver IB. "Non-random X chromosome inactivation in Aicardi syndrome." Hum Genet. 2009 March;125(2):211-6. Pubmed PMID: 19116729
- Fruhman G, Eble TN, Gambhir N, Sutton VR, Van den Veyver IB, Lewis RA. "Ophthalmologic findings in Aicardi syndrome.." J AAPOS. 2012 June;16(3):238-41. Pubmed PMID: 22681940
- Breman A, Pursley AN, Hixson P, Bi W, Ward P, Bacino CA, Shaw C, Lupski JR, Beaudet A, Patel A, Cheung SW, Van den Veyver I. "Prenatal chromosomal microarray analysis in a diagnostic laboratory; experience with >1000 cases and review of the literature." Prenat Diagn. 2012 April;32(4):351-61. Pubmed PMID: 22467166
- Emrick LT, Murphy L, Shamshirsaz AA, Ruano R, Cassady CI, Liu L, Chang F, Sutton VR, Li M, Van den Veyver IB.. "Prenatal diagnosis of CLOVES syndrome confirmed by detection of a mosaic PIK3CA mutation in cultured amniocytes." Am J Med Genet A. 2014 July 14 Pubmed PMID: 25044986
- Van den Veyver IB, Panichkul PP, Antalffy BA, Sun Y, Hunter JV, Armstrong DD. "Presence of filamin in the astrocytic inclusions of Aicardi syndrome.." Pediatr. Neurol.. 2004 January;30(1):41470. Pubmed PMID: 14738943
- Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. "Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.." Nat. Genet.. 1999 October;23(2):185-8. Pubmed PMID: 10508514