Pediatric, Developmental and Genetic Ophthalmology

• Current Research
• Staff
• Recent Publications

Current Research

Uveal coloboma is a potentially blinding, developmental abnormality of the eye caused by failure of the optic fissure to close during the 5th week of human gestation. The purpose of our clinical and basic research is to better understand the genetic and developmental mechanisms of optic fissure closure. Our short-term goal is to provide better diagnostics and genetic counseling for our patients; our long-term goal is to find preventions and/or treatments for this condition. Our approach is summarized in the following figure:

Our clinical studies are focused on understanding how patients with coloboma see and what, if any, associated clinical conditions they might have. Using state-of-the-art diagnostic equipment, we are trying to better understand the anatomy of eyes and the visual pathways of patients with coloboma. We are also collecting detailed clinical and epidemiology information.

Using the tools of Mendelian and complex genetics, we are also searching for genes important in optic fissure closure in humans. We are also using mouse models to better understand how genes are regulated during the course of optic fissure closure. Specific mutant mouse strains are also being investigated to discover genes that might cause coloboma in humans.

Staff

Name	Title	E-Mail
Brian Brooks, MD	Pediatric Ophthalmologist	brooksb@nei.nih.gov
Delphine Blain, MS, MBA	Genetic Counselor	db417p@nih.gov
Prasad Alur, Ph.D.	Lab Manager	ra215u@nih.gov
Jacob Brown, MD, Ph.D.	IRTA	brownjd@nei.nih.gov
Sanita Bharti, Ph.D	Postdoctoral Research Fellow	sanitab@nei.nih.gov
Elangovan Boobalan, Ph.D.	Research Associate	elangovanb@mail.nih.gov
Felix Onojafe, D.V.M.	Senior Lab Technician	onojafef@mail.nih.gov
Casey Ferguson, RN	Nurse Coordinator	cferguson1@nei.nih.gov
Lorenzo Nichols, B.S.	Post-Baccalaureate Student	nicholsl@mail.nih.gov

Recent Publications

1. Brooks BP, Moroi SE, Downs CA, Wiltse S, Othman MI, Semina EV, Richards JE. A novel mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome. Ophthalmic Genetics. 25:57-62 (2004).
2. Brooks BP, Kleta R, Caruso RC, Stuart C, Ludlow J, Stratakis CA. Triple-A syndrome with prominent ophthalmic features and a novel mutation in the AAAS gene: a case report. BMC Ophthalmology. 4:7 (2004).
3. Espinoza MH, Ganga M, Vadlamudi U, Martin DM, Brooks BP, Semina EV, Murray JC, Amendt BA. Protein kinase C phosphorylation modulates N- and C-terminal regulatory activities of the PITX2 homoedomain protein. Biochemistry. 44:3942-3954. (2005).
4. Brooks BP, Kleta R, Stuart C, Tuchman M, Jeong A, Stergiopoulous S, Bei T, Bjornson B, Russel L, Chanoine JP, Tsagarakis S, Kalsner LR, Stratakis CA. Genetic heterogeneity and clinical phenotype in triple-A syndrome: a review of the NIH experience 2000-2005. Clin Genetics. 68:215-221. (2005).
5. Huizing M, Brooks BP, Anikster Y. Optic atrophies in metabolic disorders. Mol Genet Metab. 86:51-60 (2005).
6. Huizing M, Brooks BP, Anikster Y. Optic neuropathies in inherited metabolic disorders. Ped Endocrin Rev. 3:97-103 (2005).
7. Alur RP, Brooks BP. Clinical and genetic analysis of coloboma: a review. Asian J Exp Sci. 20:1-15. (2006).
8. Brooks BP, Meck JC, Bendavid C, Haddad B, Blain D, Toretsky JA. Unbalanced 16p;13q translocation in a patient with factor VII deficiency and developmental abnormalities. BMC Medical Genetics. 7:2 (2006).
9. Tang J, Gokhale PA, Brooks SE, Blain D, Brooks BP. Increased corneal thickness in patients with ocular coloboma. J-AAPOS. 10:175-7 (2006).
10. Chang L, Blain D, Bertuzzi S, Brooks BP. Uveal coloboma: clinical and basic science update. Current Opinions in Ophthalmology. 17::447-70 (2006).
11. Blain D and Brooks BP. Molecular testing and genetic counseling in ophthalmology. Archives of Ophthalmology. 125:196-203 (2007).
12. Kraemer KH, Patronas NJ, Schiffmann R, Brooks BP, Tamura D, Digiovanna JJ. Xeroderma pigmentosum, trichothiodystrophy, and Cockayne syndrome: A complex genotype-phenotype relationship. Neuroscience. 145:1388-96 (2007).
13. Brooks BP, Larson DM, Chan CC, Kjellstron S, Smith RS, Crawford MA, Lamoreux L, Huizing M, Hess R, Jiao X, Hejtmancik FJ, Maminishkis A, John SWM, Bush R, Pavan WJ. Analysis of ocular hypopigmentation in Rab38cht/cht mice. Inv Ophthal Vis Sci. In press, August 2007.
14. Alur RR, Cox TA, Crawford MA, Gong X, Brooks BP. Optic nerve axon number in mouse is regulated by Pax2. J-AAPOS. In press. August 2007.
15. Blain D and Brooks BP. Molecular testing and genetic counseling in ophthalmology. Archives of Ophthalmology. 125:196-203 (2007).
16. Kraemer KH, Patronas NJ, Schiffmann R, Brooks BP, Tamura D, Digiovanna JJ. Xeroderma pigmentosum, trichothiodystrophy, and Cockayne syndrome: A complex genotype-phenotype relationship. Neuroscience. 145:1388-96 (2007).
17. Brooks BP, Larson DM, Chan CC, Kjellstron S, Smith RS, Crawford MA, Lamoreux L, Huizing M, Hess R, Jiao X, Hejtmancik FJ, Maminishkis A, John SWM, Bush R, Pavan WJ. Analysis of ocular hypopigmentation in Rab38cht/cht mice. Inv Ophthal Vis Sci. 48:3905-13 (2007).
18. MacDonald IM, Brooks BP, Sieving PA. Eyeing a new network. Science. 318:1068 (2007)
19. Doherty ES, Lacbawan F, Hadley DW, Brewer C, Zalewski C, Kim HJ, Glass P, Solomon B, Rosenbaum K, Domingo DL, Hart TC, Brooks BP, Immken L, Lowry RB, Kimonis V, Shanske AL, Knightly C, McDonald-McGinn Dm Zackai EH, Muenke M. Muenke syndrome (FGFR3-relate-craniosynostosis). Expansion of the phenotype and literature review. Am J Med Genetc. 143:3204-15 (2007)
20. Goodwin H, Brooks BP, Porter FD. Acute postnatal cataract formation in Smith-Lemli-Opitz Syndrome. Am J Med Gene, A. 146:208-11 (2008).
21. Meredith M, Gordon L, Clauss S, Sachdev V, Smith A, Perry M, Brewer C, Zalewski C, Kim J, Solomon B, Brooks BP, Gerber L, Turner M, Domingo D, Hart TC, Graf J, Reynolds J, Gropman A, Yanovski J, Collins F, Nabel E, Cannon R, Gahl W, Introne W. Comprehensive evaluation of patients with Hutchinson-Gilford progeria syndrome. NEJM. 358:592-604 (2008).
22. Alur RR, Cox TA, Crawford MA, Gong X, Brooks BP. Optic nerve axon number in mouse is regulated by Pax2 in mouse. J-AAPOS. 12:117-21 (2008).
23. Brooks BP, MacDonald IM, Tumminia SJ, Smaoui N, Blain D, Nezhuvingal AA, Sieving PA. Genomics in the Era of Molecular Ophthalmology: Reflections on the National Ophthalmic Disease Genotyping Network (eyeGENETM). Arch Ophth. 126:424-5 (2008).
24. Priya M, John JD, Tamura D, Brahim JS, Hornyak TJ, Stern JB, Lee CR, Khan SG, Brooks BP, Smith JA, Driscoll BP, Montemarano AD, Sugarman K, Kraemer KH. Skin cancers, blindness, and anterior tongue mass in African brothers. J Acad Derm. 59:881-6 (2008).
25. Asai-Coakwell M, French CR, Ye M, Garcha K, Bigot K, Perena AG, Staehling-Hamptom K, Mema S, Chanda B, Mushegian A, Bamforth S, Doschak MR, Li G, Dobbs MB, Giampietro PF, Brooks BP, Vijayalakshmi P, Sauvei Y, Abitbol M, Sundaresan P, van Heyningen V, Pourquie O, Underhill TM, Waskiewicz AJ, Lehmann OJ. Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotype. Hum Molec Genetics. In press, December 2008.
26. Brown JD, Duuta S, Bharti K, Bonner RF, Munson PJ, Dawid IB, Akhtar AL, Onojafe IF, Alur RP, Gross JM, Hejtmancik JF, Jiao X, Chan WY, Brooks BP. Expression profiling during ocular development identifies two Nlz genes with a critical role in optic fissure closure. Proc National Acad Sci, USA. In press, December 2008.