Associate Professor, Departments of Obstetrics & Gynecology and Molecular and Human Genetics
Interim Director, Division of Maternal-Fetal Medicine
Co-Director, Graduate Program in Translational Biology and Molecular Medicine

M.D., University of Antwerp, Belgium, 1986
Resident in Obstetrics and Gynecology, University of Antwerp Affiliated Hospitals, Belgium, 1991
Fellow in Maternal-Fetal Medicine, Baylor College of Medicine, 1993
Fellow in Genetics, Baylor College of Medicine, 1996

RESEARCH INTERESTS:

In my lab's first project, we focus on the identification of the genes mutated in Aicardi syndrome (AIC) and Goltz syndrome or focal dermal hypoplasia (FDH), two severe X-linked disorders that only or primarily affect girls. Children with AIC have typical developmental defects of eyes and brain, severe seizures and mental retardation. FDH patients have skin, eye and skeletal defects. We have collected DNA samples from patients to search for the mutated gene by mutation analysis of candidate genes and by comparative genomic hybridization on DNA microarrays. These studies led to our recent discovery that PORCN, encoding the human homolog of Drosophila porcupine which is essential for secretion of Wnt proteins, is the gene that is mutated in FDH. We are now embarking on the functional analysis of the consequence of mutations in PORCN using animal models and cell culture systems. Detailed clinical phenotyping studies in AIC are ongoing concurrently in collaboration with other investigators in the department (Dr. V. Reid Sutton, Dr. Richard A. Lewis).

In the second project, we study complete hydatidiform moles (CHM), an abnormal development of human pregnancy with a hyperplastic placenta and no fetus. Most sporadic CHM are diploid androgenetic: their entire genome is paternally inherited. This suggests that imbalance between expression of paternally and maternally imprinted genes causes CHM. Rare recurrent HMs have normal biparentally inherited diploid genomes (BiHM), but show a generalized defect of reprogramming of imprinting. The women who have these BiHM pregnancies have an autosomal recessive mutation. A major locus was mapped to 19q13.4, and recently mutations in NLRP7 were described in women with BiHM. We confirmed mutations in patients studied in our lab and are now focusing on characterizing the function of NLRP7 to understand how it can lead to disturbances of imprinting, BiHM and other reproductive failure. For the second part of our CHM project, we perform methylation and expression screens on DNA and RNA from typical androgenetic CHMs to find new imprinted genes that have placenta-specific imprinting. These may be important for fetal nutrition and placental function in general.

In the third project, we are focusing on epigenetic gene regulation during development. We study in mice whether DNA methylation can be influenced by diets that are enriched for or depleted in methyl donors, such as folic acid, given at different stages of development. We study long term changes in DNA methylation and gene expression in these mice. To screen the genome for methylated CpGs, we use known tools, such as restriction landmark genome scanning (RLGS) and are generating a microarray for methylation screening of the mouse genome. Using the same strategy, we also study in mice the epigenetic effects of diets with high or low protein content. These studies are relevant to understanding the contribution of nutritional imbalance to the developmental origin of common adult-onset disorders.

SELECTED PUBLICATIONS:

1. Kou YC, Shao L, Peng HH, Rosetta R, del Gaudio D, Wagner AF, Al-Hussaini TK, Van den Veyver IB (2008). A recurrent intragenic genomic duplication, other novel mutations in NLRP7 and imprinting defects in recurrent biparental hydatidiform moles. Mol. Hum. Reprod. 14: 33-40.

2. Wang X*, Sutton VR*, Peraza O, Yu Z, Rosetta R, Kou YC, Eble TN, Patel A, Thaller C, Fang P, Van den Veyver IB (2007). Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia. Nat. Genet. 39: 836-838. (*equal contribution)

3. Glasmacher MA, Sutton VR, Hopkins B, Eble T, Lewis RA, Park Parsons D, Van den Veyver IB (2006). Phenotype and Management of Aicardi Syndrome: New Findings from a Survey of 75 Children. J. Child. Neurol. 22: 176-184.

4. Van den Veyver IB, Al-Hussaini TK (2006). Biparental hydatidiform moles: a maternal effect mutation affecting imprinting in the offspring. Hum. Reprod. Update 12: 233-242.

5. Sutton VR, Hopkins BJ, Gambhir N, Lewis RA, Van den Veyver IB (2005). Facial and Physical Features of Aicardi Syndrome: Infants to Teenagers. Am. J. Med. Genet. 138: 254-258.

6. Yu L, Liu C, Bennett K, Wu YZ, Dai Z, Vandeusen J, Opavsky R, Raval A, Trikha P, Rodriguez B, Becknell B, Mao C, Lee S, Davuluri RV, Leone G, Van den Veyver IB, Caligiuri MA, Plass C (2004). A Notl-EcoRV promoter library for studies of genetic and epigenetic alterations in mouse models of human malignancies. Genomics 84: 647-660.

7. Prakash, SK, Cormier TA, McCall AM, Garcia JJ, Sierra R, Haupt B, Zoghbi HY, Van den Veyver IB (2002). Loss of holocytochrome c-type synthetase (HCCS) causes the male lethality and most features of X-linked dominant Microphthalmia with Linear Skin defects (MLS) syndrome. Hum. Mol. Genet. 11: 3237-3248.

8. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23: 185-188.

9. Bou Maglabey Y, Kircheisen R, Seoud M, El-Mogharbel N, Van den Veyver IB, Slim R (1999). Genetic mapping of a maternal locus responsible for familial hydatidiform moles. Hum. Mol. Genet. 8: 667-671.

For more publications, see listing on Pub Med.

CONTACT INFORMATION:

Ignatia B. Van den Veyver, M.D.
Department of Obstetrics and Gynecology
Department of Molecular and Human Genetics
Medical Towers
1709 Dryden, Suite 1100
Houston, Texas 77030, U.S.A.
Mail Stop: BCM610

Phone: 713-798-4914
Fax: 713-798-5997
E-mail:
Web site: http://www.bcm.edu/genetics/vandenveyver/

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