Research Biographies

PROFESSOR DAVID FITZPATRICK MD, FRCP(Edin)

Medical and Developmental Genetics

Head of Medical and Developmental Genetics (Joint with Ian Jackson)

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

• Murray JE, Walayat M, Gillett P, Sharkey FH, Rajan D, Carter NP, Fitzpatrick DR: An atypical facial appearance and growth pattern in a child with Cornelia de Lange Syndrome: an intragenic deletion predicting loss of the N-terminal region of NIPBL
  Clin Dysmorphol 21:22-23, 2012. PubMed Abstract
• Fakhouri WD, Rhea L, Du T, Sweezer E, Morrison H, Fitzpatrick D, Yang B, Dunnwald M, Schutte BC: MCS9.7 Enhancer activity is highly, but not completely, associated with expression of Irf6 and p63 Dev Dyn 241:i, 2012. PubMed Abstract
• Wu W, Tiesinga PH, Tucker TR, Mitroff SR, Fitzpatrick D: Dynamics of population response to changes of motion direction in primary visual cortex
  J Neurosci 31:12767-12777, 2011. Pubmed Abstract
• Lettice LA, Daniels S, Sweeney E, Venkataraman S, Devenney PS, Gautier P, Morrison H, Fantes J, Hill RE, FitzPatrick DR: Enhancer-adoption as a mechanism of human developmental disease. Hum Mutat 32:1492-1499, 2011PubMed Abstract
• Snape K, Hanks S, Ruark E, Barros-Nunez P, Elliott A, Murray A, Lane AH, Shannon N, Callier P, Chitayat D, Clayton-Smith J, Fitzpatrick DR, Gisselsson D, Jacquemont S, Asakura-Hay K, Micale MA, Tolmie J, Turnpenny PD, Wright M, Douglas J, Rahman N: Mutations in CEP57 cause mosaic variegated aneuploidy syndrome. Nat Genet 43:527-529, 2011. PubMed Abstract
• Rainger J, van BE, Ramsay JK, McKie L, Al-Gazali L, Pallotta R, Saponari A, Branney P, Fisher M, Morrison H, Bicknell L, Gautier P, Perry P, Sokhi K, Sexton D, Bardakjian TM, Schneider AS, Elcioglu N, Ozkinay F, Koenig R, Megarbane A, Semerci CN, Khan A, Zafar S, Hennekam R, Sousa SB, Ramos L, Garavelli L, Furga AS, Wischmeijer A, Jackson IJ, Gillessen-Kaesbach G, Brunner HG, Wieczorek D, van BH, Fitzpatrick DR: Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice. PLoS Genet 7(7):e1002114, 2011.
  PubMed Abstract
  
• Lynch SA, Foulds N, Thuresson AC, Collins AL, Anneren G, Hedberg BO, Delaney CA, Iremonger J, Murray CM, Crolla JA, Costigan C, Lam W, Fitzpatrick DR, Regan R, Ennis S, Sharkey F: The 12q14 microdeletion syndrome: six new cases confirming the role of HMGA2 in growth. Eur J Hum Genet 19(5):534-539, 2011.PubMed Abstract
• Southgate L, Machado RD, Snape KM, Primeau M, Dafou D, Ruddy DM, Branney PA, Fisher M, Lee GJ, Simpson MA, He Y, Bradshaw TY, Blaumeiser B, Winship WS, Reardon W, Maher ER, Fitzpatrick DR, Wuyts W, Zenker M, Lamarche-Vane N, Trembath RC: Gain-of-function mutations of ARHGAP31, a Cdc42/Rac1 GTPase regulator, cause syndromic cutis aplasia and limb anomalies. Am J Hum Genet 88:574-585, 2011. PubMed Abstract
• Gohring, I.; Tagariello, A.; Endele, S.; Stolt, C.C.; Ghassibe, M.; Fisher, M.; Thiel, C.T.; Trautmann, U.; Vikkula, M.; Winterpacht, A.; Fitzpatrick, D.R. and Rauch, A. Disruption of ST5 is associated with mental retardation and multiple congenital anomalies.
  J Med Genet. 47(2):91-98, 2010 PubMed Abstract
• 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