Research Biographies

PROFESSOR DAVID FITZPATRICK MD, FRCP(Edin)

Medical and Developmental Genetics

Programme Leader

Contact Details

Research Areas

Identifying Genes that cause Human Malformations

My research aims to understand the genes that cause specific human birth defects and then study how these genes function during development. We study children with specific malformations either of the eye (small eyes aka microphthalmia, and absent eyes aka anophthalmia) or of the facial region (cleft lip and cleft palate).

Key/Selected Publications

• Fantes, J.A.; Boland, E.; Ramsay, J.; Donnai, D.; Splitt, M.; Goodship, J.A.; Stewart, H.; Whiteford, M.; Gautier, P.; Harewood, L.; Holloway, S.; Sharkey, F.; Maher, E.; van Heyningen, V.; Clayton-Smith, J.; FitzPatrick, D.R. and Black GC. FISH mapping of de novo apparently balanced chromosome rearrangements identifies characteristics associated with phenotypic abnormality. Am J Hum Genet 82(4):916-26, 2008 PubMed Abstract
• Williamson K.A.; Hever, A.M.; Rainger, J.; Rogers, R.C.; Magee, A.; Fiedler, Z.; Keng, W.T.; Sharkey, F.H.; McGill, N.; Hill, C.J.; Schneider, A.; Messina, M.; Turnpenny, P.D.; Fantes, J.A.; van Heyningen, V. and FitzPatrick DR. Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome. Hum Mol Genet 15:1413-22, 2006 PubMed Abstract
• Ragge, N.K.; Brown A.G.; Poloschek, C.M.; Lorenz, B.; Henderson R.A.; Clarke, M.P.; Russell-Eggitt, I.; Fielder, A.; Gerrelli, D.; Martinez-Barbera, J.P.; Ruddle, P.; Hurst, J.; Collin, J.R.; Salt, A.; Cooper, S.T.; Thompson, P.J.; Sisodiya, S.M.; Williamson, K.A.; FitzPatrick, D.R.; van Heyningen, V. and Hanson, I.M. Heterozygous mutations of OTX2 cause severe ocular malformations. Am J Hum Genet 76(6):1008-22, 2005 PubMed Abstract
• Ragge, N. K.; Lorenz, B.; Schneider, A.; Bushby, K.; de Sanctis, L.; de Sanctis, U.; Salt, A.; Collin, J. R.; Vivian, A. J.; Free, S. L.; Thompson, P.; Williamson, K.A.; Sisodiya, S.M.; van Heyningen, V. and Fitzpatrick, D.R. . SOX2 Anophthalmia Syndrome. Am J Med Genet A 135(1):1-7, 2005 PubMed Abstract
• Fantes, J.; Ragge, N. K.; Lynch, S. A.; McGill, N. I.; Collin, J. R.; Howard-Peebles, P. N.; Hayward, C.; Vivian, A. J.; Williamson, K.; Van Heyningen, V. and FitzPatrick, D. R. Mutations in SOX2 cause anophthalmia. Nat Genet 33:461-463, 2003 PubMed Abstract
• FitzPatrick, D. R.; Carr, I. M.; McLaren, L.; Leek, J. P.; Wightman, P.; Williamson, K.; Gautier, P.; McGill, N.; Hayward, C.; Firth, H.; Markham, A.F.; Fantes, J.A. and Bonthron, D.T. Identification of SATB2 as the cleft palate gene on 2q32-q33. Hum Mol Genet 12:2491-2501, 2003
  PubMed Abstract
• Brewer, C.; Holloway, S.; Zawalnyski, P.; Schinzel, A. and FitzPatrick, D. A chromosomal deletion map of human malformations. Am J Hum Genet 63:1153-1159, 1998 PubMed Abstract

Recent Publications

• Harewood, L.; Keeling, J.W.; Fantes, J.A.; Opitz, J.M. and Fitzpatrick, D.R. 'Crommelin-type' symmetrical tetramelic reduction deformity: a new case and breakpoint mapping of a reported case with de-novo t(2;12)(p25.1;q23.3). Clin.Dysmorphol. 19(1):5-13, 2010 PubMed Abstract
• Benko, S.; Fantes, J.A.; Amiel, J.; Kleinjan, D.J.; Thomas, S.; Ramsay, J.; Jamshidi, N.; Essafi, A.; Heaney, S.; Gordon, C.T.; McBride, D.; Golzio, C.; Fisher, M.; Perry, P.; Abadie, V.; Ayuso, C.; Holder-Espinasse, M.; Kilpatrick, N.; Lees, M.M.; Picard, A.; Temple, I.K.; Thomas, P.; Vazquez, M.P.; Vekemans, M.; Crollius, H.R.; Hastie, N.D.; Munnich, A.; Etchevers, H.C.; Pelet, A.; Farlie, P.G.; Fitzpatrick, D.R. and Lyonnet, S. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence. Nat.Genet. 41(3):359-364, 2009 PubMed Abstract
• Clayton-Smith, J.; Walters, S.; Hobson, E.; Burkitt-Wright, E.; Smith, R.; Toutain, A.; Amiel, J.; Lyonnet, S.; Mansour, S.; Fitzpatrick, D.; Ciccone, R.; Ricca, I.; Zuffardi, O. and Donnai, D. Xq28 duplication presenting with intestinal and bladder dysfunction and a distinctive facial appearance.
  Eur.J.Hum.Genet. 17(4):434-443, 2009 PubMed Abstract
• Gordon, C.T.; Tan, T.Y.; Benko, S.; Fitzpatrick, D.; Lyonnet, S. and Farlie, P.G. Long-range regulation at the SOX9 locus in development and disease. J Med Genet. 46(10):649-656, 2009 PubMed Abstract
• Henderson, R.H.; Williamson, K.A.; Kennedy, J.S.; Webster, A.R.; Holder, G.E.; Robson, A.G.; Fitzpatrick, D.R.; van, H., V and Moore, A.T. A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction. Mol.Vis. 15:2442-2447, 2009
  PubMed Abstract
• Hilton, E.; Johnston, J.; Whalen, S.; Okamoto, N.; Hatsukawa, Y.; Nishio, J.; Kohara, H.; Hirano, Y.; Mizuno, S.; Torii, C.; Kosaki, K.; Manouvrier, S.; Boute, O.; Perveen, R.; Law, C.; Moore, A.; Fitzpatrick, D.; Lemke, J.; Fellmann, F.; Debray, F.G.; Dastot-Le-Moal, F.; Gerard, M.; Martin, J.; Bitoun, P.; Goossens, M.; Verloes, A.; Schinzel, A.; Bartholdi, D.; Bardakjian, T.; Hay, B.; Jenny, K.; Johnston, K.; Lyons, M.; Belmont, J.W.; Biesecker, L.G.; Giurgea, I. and Black, G. BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects. Eur.J Hum.Genet. 17(10):1325-1335, 2009
  PubMed Abstract
  
• Fantes, J.A.; Boland, E.; Ramsay, J.; Donnai, D.; Splitt, M.; Goodship, J.A.; Stewart, H.; Whiteford, M.; Gautier, P.; Harewood, L.; Holloway, S.; Sharkey, F.; Maher, E.; van Heyningen, V.; Clayton-Smith, J.; Fitzpatrick, D.R. and Black, G.C. FISH mapping of de novo apparently balanced chromosome rearrangements identifies characteristics associated with phenotypic abnormality.
  Am J Hum Genet 82(4):916-926, 2008 PubMed Abstract
• Little, J.; Gilmour, M.; Mossey, P.A.; Fitzpatrick, D.; Cardy, A.; Clayton-Smith, J. and Fryer, A.E. Folate and clefts of the lip and palate--a U.K.-based case-control study: Part I: Dietary and supplemental folate. Cleft Palate Craniofac J 45(4):420-427, 2008 PubMed Abstract
• Little, J.; Gilmour, M.; Mossey, P.A.; Fitzpatrick, D.; Cardy, A.; Clayton-Smith, J.; Hill, A.; Duthie, S.J.; Fryer, A.E.; Molloy, A.M. and Scott, J.M. Folate and clefts of the lip and palate--a U.K.-based case-control study: Part II: Biochemical and genetic analysis.
  Cleft Palate Craniofac J 45(4):428-438, 2008 PubMed Abstract
• Prabhakar, S.; Visel, A.; Akiyama, J.A.; Shoukry, M.; Lewis, K.D.; Holt, A.; Plajzer-Frick, I.; Morrison, H.; Fitzpatrick, D.R.; Afzal, V.; Pennacchio, L.A.; Rubin, E.M. and Noonan, J.P. Human-specific gain of function in a developmental enhancer. Science 321(5894):1346-1350, 2008 PubMed Abstract
• Rahimov, F.; Marazita, M.L.; Visel, A.; Cooper, M.E.; Hitchler, M.J.; Rubini, M.; Domann, F.E.; Govil, M.; Christensen, K.; Bille, C.; Melbye, M.; Jugessur, A.; Lie, R.T.; Wilcox, A.J.; Fitzpatrick, D.R.; Green, E.D.; Mossey, P.A.; Little, J.; Steegers-Theunissen, R.P.; Pennacchio, L.A.; Schutte, B.C. and Murray, J.C. Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip. Nat Genet 40(11):1341-1347, 2008 PubMed Abstract
• Schneider, A.; Bardakjian, T.M.; Zhou, J.; Hughes, N.; Keep, R.; Dorsainville, D.; Kherani, F.; Katowitz, J.; Schimmenti, L.A.; Hummel, M.; Fitzpatrick, D.R. and Young, T.L. Familial recurrence of SOX2 anophthalmia syndrome: phenotypically normal mother with two affected daughters.
  Am J Med Genet A 146A(21):2794-2798, 2008 PubMed Abstract
• Boland, E.; Clayton-Smith, J.; Woo, V.G.; McKee, S.; Manson, F.D.; Medne, L.; Zackai, E.; Swanson, E.A.; Fitzpatrick, D.; Millen, K.J.; Sherr, E.H.; Dobyns, W.B. and Black, G.C. Mapping of deletion and translocation breakpoints in 1q44 implicates the serine/threonine kinase AKT3 in postnatal microcephaly and agenesis of the corpus callosum.
  Am J Hum Genet 81(2):292-303, 2007 PubMed Abstract
• Fitzpatrick, D. R. Genetic Metabolic Disease. In: Fetal and Neonatal Pathology. Keeling, J. W. and Khong, T. T. (eds.) 4th Edition, Springer, London, 162-183, 2007
• Henderson, R.A.; Williamson, K.; Cumming, S.; Clarke, M.P.; Lynch, S.A.; Hanson, I.M.; Fitzpatrick, D.R.; Sisodiya, S. and van Heyningen, V. Inherited PAX6, NF1 and OTX2 mutations in a child with microphthalmia and aniridia. European Journal of Human Genetics 15(8):898-901, 2007 PubMed Abstract
• Kalscheuer, V.M.; Fitzpatrick, D.; Tommerup, N.; Bugge, M.; Niebuhr, E.; Neumann, L.M.; Tzschach, A.; Shoichet, S.A.; Menzel, C.; Erdogan, F.; Arkesteijn, G.; Ropers, H.H. and Ullmann, R. Mutations in autism susceptibility candidate 2 (AUTS2) in patients with mental retardation.
  Hum Genet 121(3-4):501-509, 2007 PubMed Abstract
• Kline, A.D.; Krantz, I.D.; Sommer, A.; Kliewer, M.; Jackson, L.G.; Fitzpatrick, D.R.; Levin, A.V. and Selicorni, A. Cornelia de Lange syndrome: clinical review, diagnostic and scoring systems, and anticipatory guidance. Am J Med Genet A 143(12):1287-1296, 2007 PubMed Abstract
• Lirussi, F.; Jonard, L.; Gaston, V.; Sanlaville, D.; Kooy, R.F.; Winnepenninckx, B.; Maher, E.R.; Fitzpatrick, D.R.; Gicquel, C.; Portnoi, M.F.; Couderc, R.; Vazquez, M.P. and Bahuau, M. Beckwith-Wiedemann-like macroglossia and 18q23 haploinsufficiency.
  Am J Med Genet A 143(23):2796-2803, 2007 PubMed Abstract
• Pasutto, F.; Sticht, H.; Hammersen, G.; Gillessen-Kaesbach, G.; Fitzpatrick, D.R.; Nurnberg, G.; Brasch, F.; Schirmer-Zimmermann, H.; Tolmie, J.L.; Chitayat, D.; Houge, G.; Fernandez-Martinez, L.; Keating, S.; Mortier, G.; Hennekam, R.C.; von der, W.A.; Slavotinek, A.; Meinecke, P.; Bitoun, P.; Becker, C.; Nurnberg, P.; Reis, A. and Rauch, A. Mutations in STRA6 cause a broad spectrum of malformations including anophthalmia, congenital heart defects, diaphragmatic hernia, alveolar capillary dysplasia, lung hypoplasia, and mental retardation. Am J Hum Genet 80(3):550-560, 2007 PubMed Abstract
• Suri, M.; Kelehan, P.; O'Neill, D.; Vadeyar, S.; Grant, J.; Ahmed, S.F.; Tolmie, J.; McCann, E.; Lam, W.; Smith, S.; Fitzpatrick, D.; Hastie, N.D. and Reardon, W. WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations. Am J Med Genet A 143(19):2312-2320, 2007 PubMed Abstract
• Verma, A.S. and Fitzpatrick, D.R. Anophthalmia and microphthalmia. Orphanet J Rare Dis 2:47, 2007 PubMed Abstract
• Winnepenninckx, B.; Debacker, K.; Ramsay, J.; Smeets, D.; Smits, A.; Fitzpatrick, D.R. and Kooy, R.F. CGG-Repeat Expansion in the DIP2B Gene is Associated with the Fragile Site FRA12A on Chromosome 12q13.1. Am J Hum Genet 80:221-231, 2007 PubMed Abstract