HOME | ABOUT | SERVICES | HEALTH INFO | RESEARCH | PATIENTS + VISITORS | CAREERS | MEDIA | SUPPORT WCH
Neurogenetics Research ProgramIdentification of genes and understanding of molecular mechanisms leading to intellectual disability represents a challenge of significant medical importance. Our focus on syndromic and non-syndromic forms of X-chromosome linked intellectual disability (XLMR) extends the work carried out in the Department on fragile X syndrome. We identified the first gene for non-syndromic intellectual disability (MRX) in 1996 (the FMR2 gene). Several other MRX genes (PAK3, RSK2, alpha PIX and ARX), candidate MRX genes (FHF2, GRIA3, KFL8) as well as genes for syndromic forms of XLMR (MRXS; BFLS, ATRX gene mutation in SFM syndrome, CDKL5 in Rett syndrome) have been identified since. We might be seen primarily as a gene discovery group, however, our focus is gradually shifting towards functional characterisation of the novel MRX/MRXS genes (including animal and cellular models) and their role in molecular processes underpinning human cognitive function. We are also involved in studies of other X-linked disorders. In 1999 we identified the gene for spondyloepiphyseal dysplasia tarda (SEDL; disorder of bone growth), and more recently characterised its function and spectrum of mutations. We have an ongoing collaboration with A/Prof. Jamie Craig from Flinders University , Adelaide on cataract genetics and also tackle the gene discovery for X-linked cutaneous amyloidosis or reticulate pigmentary disorder (XLCA/PRD). Current researchOur main research focus is isolation and further characterisation of genes implicated in various forms of intellectual disability. We have a range of projects addressing various aspects of this work. Some of these include:
Key personnelResearch staffProfessor Jozef Gécz, PhD Dr. Cheryl Shoubridge Dr. Mark Corbett Ms. Marie Shaw Ms. Lucianne Vandeleur Ms. Alison Gardner Mr. Sonny Nguyen Mr. Lachlan Jolly Ms. Tulika Bose Huang Lingli Ms. Lynne Hobson Postgraduate StudentsKim Hynes May Tan Stanley Tan Recent publicationsGécz J, Gedeon AG, Sutherland GR, Mulley JC Identification of FMR2 : A gene associated with FRAXE mental retardation. Nature Genetics 13:105-108, 1996. IF=26.49, SCI=131 Strømme P, Mangelsdorf ME, Shaw MA, Lower KM, Lewis SM, Bruyere H, Lutcherath V, Gedeon AK, Wallace RH, Scheffer IE, Turner G, Partington M, Frints SG, Fryns JP, Sutherland GR, Mulley JC, Gécz J Mutations of the human ortholog of Aristaless cause X-linked mental retardation and epilepsy. Nature Genetics 30: 441-445, 2002. IF=26.49 , SCI=60 JG89. McKenzie O, Ponte I, Mangelsdorf M, Finnis M, Stifani S, Shoubridge C, Gécz J, Broccoli V. ARX, the gene responsible for West syndrome and related disorders, is a groucho/transducin-like enhancer of split (TLE) dependent transcriptional repressor. Neuroscience 146(1):236-247, 2007. IF= 3.41 (3) JG90. Shoubridge C, Cloosterman D, Parkinson–Lawrence E, Brooks D, Gécz J. Molecular pathology of mutations in the ARX homeobox gene. Genomics, 90(1):59-71, 2007. IF= 3.2 (3) JG93. Raymond FL, Tarpey PS, Edkins S, Tofts C, O'Meara S, Teague J, Butler A, Stevens C, Barthorpe S, Buck G, Cole J, Dicks E, Gray K, Halliday K, Hills K, Hinton J, Jones D, Menzies A, Perry J, Raine K, Shepherd R, Small A, Varian J, Widaa S, Mallya U, Moon J, Luo Y, Shaw M, Boyle J, Kerr B, Turner G, Quarrell O, Cole T, Easton DF, Wooster R, Bobrow M, Schwartz CE, Gecz J, Stratton MR, Futreal PA. Mutations in ZDHHC9, which encodes a palmitoyltransferase of NRAS and HRAS, cause X-linked mental retardation associated with a Marfanoid habitus. American Journal of Human Genetics 80(5):982-987, 2007. IF=12.65 (8) JG95. Voss AK, Gamble R, Collin C, Shoubridge C, Corbett M, Gecz J, Thomas T. Protein and gene expression analysis of Phf6, the gene mutated in the Borjeson-Forssman-Lehmann Syndrome of intellectual disability and obesity. Gene Expression Patterns 7(8):858-871, 2007. IF=2.0 JG96. Tarpey PS, Raymond FL, Nguyen LS, Rodriguez J, Hackett A, Vandeleur L, Smith R, Shoubridge C, Edkins S, Stevens C, O'Meara S, Tofts C, Barthorpe S, Buck G, Cole J, Halliday K, Hills K, Jones D, Mironenko T, Perry J, Varian J, West S, Widaa S, Teague J, Dicks E, Butler A, Menzies A, Richardson D, Jenkinson A, Shepherd R, Raine K, Moon J, Luo Y, Parnau J, Bhat SS, Gardner A, Corbett M, Brooks D, Thomas P, Parkinson-Lawrence E, Porteous ME, Warner JP, Sanderson T, Pearson P, Simensen RJ, Skinner C, Hoganson G, Superneau D, Wooster R, Bobrow M, Turner G, Stevenson RE, Schwartz CE, Futreal PA, Srivastava AK, Stratton MR, Gécz J. Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nature Genetics 39(9):1127-1133, 2007. IF= 25.8 (8) JG97. Butcher CM, Hahn U, To LB, Gécz J, Wilkins EJ, Scott HS, Bardy PG, D'Andrea RJ. Two novel JAK2 exon 12 mutations in JAK2V617F-negative polycythaemia vera patients. Leukemia 22(4):870-3, 2008. IF=6.15 JG100. Turner G, Boyle J, Partington M, Kerr B, Raymond L, Gécz J and Members of the GOLD teams. Restoring reproductive confidence in families with X-linked mental retardation. Clinical Genetics, 73(2):188-90, 2008. IF=3.3 JG101. Froyen G, Corbett M, Vandewalle J, Jarvela I, Lawrence O, Meldrum C, Bauters M, Govaerts K, Vandeleur L, Van Esch H, Chelly J, Sanlaville D, van Bokhoven H, Ropers HH, Laumonnier F, Ranieri E, Schwartz CE, Abidi F, Tarpey PS, Futreal PA, Whibley A, Raymond FL, Stratton MR, Fryns JP, Scott R, Peippo M, Sipponen M, Partington M, Mowat D, Field M, Hackett A, Marynen P, Turner G, Gécz J, Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation. American Journal of Human Genetics 82(2):432-43, 2008. IF=12.65 (1) JG102. Scheffer IE, Turner SJ, Dibbens LM, Bayly MA, Friend K, Hodgson B, Burrows L, Shaw M, Wei C, Ullmann R, Ropers HH, Szepetowski P, Haan E, Mazarib A, Afawi Z, Neufeld MY, Andrews PI, Wallace G, Kivity S, Lev D, Lerman-Sagie T, Derry CP, Korczyn AD, Gécz J, Mulley JC, Berkovic SF. Epilepsy and mental retardation limited to females: an under-recognized disorder. Brain 131(Pt 4):918-27, 2008. IF=7.62 (2 JG103. Dibbens LM, Tarpey PS, Hynes K, Bayly MA, Scheffer IE, Smith R, Bomar J, Sutton E, Vandeleur L, Shoubridge C, Edkins S, Turner SJ, Stevens C, O’Meara S, Tofts C, Barthorpe S, Buck G, Cole J, Halliday K, Jones D, Lee R, Madison M, Mironenko T, Varian J, West S, Widaa S, Wray P, Teague J, Dicks E, Butler A, Menzies A, Jenkinson A, Sheperd R, Gusella JF, Afawi Z, Mazarib A, Neufeld MY, Kivity S, Lev D, Lerman-Sagie T, Korczyn AD, Derry CP, Sutherland GR, Friend K, Shaw M, Corbett M, Hyong-Goo K, Geschwind D H, Thomas P, Haan E, Ryan S, McKee S, Berkovic SF, Futreal PA, Stratton MR, Mulley JC, Gécz J. (2008). Protocadherin 19 mutations cause sex-limited epilepsy and cognitive impairment. Nature Genetics 40(6):776-81, 2008. IF=24.2 JG104. Gilfillan GD, Selmer KK, Roxrud I, Smith R, Kyllerman M, Eiklid K, Kroken M, Mattingsdal M, Egeland T, Stenmark H, Sjøholm H, Server A, Samuelsson L, Christianson A, Tarpey P, Whibley A, Stratton MR, Futreal PA, Teague J, Edkins S, Gécz J, Turner G, Raymond FL, Schwartz C, Stevenson RE, Undlien DE, Strømme P. SLC9A6 Mutations Cause X-Linked Mental Retardation, Microcephaly, Epilepsy, and Ataxia, a Phenotype Mimicking Angelman Syndrome. American Journal of Human Genetics 82(4):1003-10, 2008. IF=12.6 JG105. Molinari F, Foulquier F, Tarpey PS, Morelle W, Boissel S, Teague J, Edkins S, Futreal PA, Stratton MR, Turner G, Matthijs G, Gécz J, Munnich A, Colleaux L. (2008) Oligosaccharyltransferase subunits mutations in non-syndromic mental retardation. American Journal of Human Genetics 82(5):1150-7, 2008. IF=12.6 (1) JG107. Jaeckle Santos LJ, Xing C, Barnes RB, Ades LC, Megarbane A, Vidal C, Xuereb A, Tarpey PS, Smith R, Khazab M, Shoubridge C, Partington M, Futreal A, Stratton MR, Gécz J, Zinn AR. Refined mapping of X-linked reticulate pigmentary disorder and sequencing of candidate genes. Human Genetics 123(5):469-76, 2008. IF=3.66 JG108. Craig JE, Friend KL, Gécz J, Rattray KM, Troski M, Mackey DA, Burdon KP. A novel locus for X-linked congenital cataract on Xq24. Molecular Vision 14:721-6, 2008. IF=2.38 JG109. Peat RA, Gécz J, Fallon JR, Tarpey PS, Smith R, Futreal A, Stratton MR, Lamandé SR, Yang N, North KN. Exclusion of biglycan mutations in a cohort of patients with neuromuscular disorders. Neuromuscular Disorders 18(8):606-9, 2008. IF=2.67 JG112. Bensaid M, Melko M, Bechara EG, Davidovic L, Berretta A, Catania MV, Gécz J, Lalli E, Bardoni B. FRAXE-associated mental retardation protein (FMR2) is an RNA-binding protein with high affinity for G-quartet RNA forming structure. Nucleic Acids Res. 2009 Jan 9. [Epub ahead of print] IF=7.55 JG113. Laumonnier F, Shoubridge C, Antar C, Nguyen LS, Van Esch H, Kleefstra T, Briault S, Fryns JP, Hamel B, Chelly J, Ropers HH, Ronce N, Blesson S, Moraine C, Gécz J, Raynaud M: Mutations of the UPF3B gene, which encodes a protein widely expressed in neurons, are associated with non-specific mental retardation with or without autism. Molecular Psychiatry, 2009 Feb 24. [Epub ahead of print] IF=10.9 JG116. Tarpey PS, Smith R, Pleasance E, Whibley A, Edkins S, Hardy C, O'Meara S, Latimer C, Dicks E, Menzies A, Stephens P, Blow M, Greenman C, Xue Y, Tyler-Smith C, Thompson D, Gray K, Andrews J, Barthorpe S, Buck G, Cole J, Dunmore R, Jones D, Maddison M, Mironenko T, Turner R, Turrell K, Varian J, West S, Widaa S, Wray P, Teague J, Butler A, Jenkinson A, Jia M, Richardson D, Shepherd R, Wooster R, Tejada MI, Martinez F, Carvill G, Goliath R, de Brouwer AP, van Bokhoven H, Van Esch H, Chelly J, Raynaud M, Ropers HH, Abidi FE, Srivastava AK, Cox J, Luo Y, Mallya U, Moon J, Parnau J, Mohammed S, Tolmie JL, Shoubridge C, Corbett M, Gardner A, Haan E, Rujirabanjerd S, Shaw M, Vandeleur L, Fullston T, Easton DF, Boyle J, Partington M, Hackett A, Field M, Skinner C, Stevenson RE, Bobrow M, Turner G, Schwartz CE, Gecz J, Raymond FL, Futreal PA, Stratton MR. A systematic, large-scale resequencing screen of X- chromosome coding exons in mental retardation. Nature Genetics, 2009 May;41(5):535-43. Epub 2009 Apr 19. IF=25.5 (2009) IF - impact factor (as published in 2009) Invited reviewsGécz J and Mulley, JC Genes for cognitive function: Developments on the X. Genome research 10:157-163, 2000.IF=9.64 ,SCI=25 Gécz J The FMR2 gene, FRAXE and non-specific X-linked mental retardation: clinical and molecular aspects. Annals of Human Genetics 64(2):95-106, 2000. IF=3.10, SCI=25 Lower K, Mangelsdorf M, Gécz J Molecular genetics of mental retardation: A complex picture emerging. Expert Reviews in Molecular Diagnostics 1(2):89-94, 2001. IF not available yet. Marshall Graves JA, Gécz J and Hameister H Evolution of the human X - a smart and sexy chromosome that controls speciation and development . Cytogenetics and Genome Research 99(1-4):141-5, 2002. IF=0.50 Savarirayan R, Thompson E and Gécz J Spondylo-epiphyseal dysplasia tarda (SEDL, MIM #313400). European Journal of Human Genetics 11(9):639-42, 2003. IF=3.67 Gécz J Sutherland GR. Preface. Cytogenetics and Genome Research 100(1-4):5-6, 2003. IF=0.50 Gécz J The molecular basis of intellectual disability: novel genes with naturally occurring mutations causing altered gene expression in the brain. Frontiers in Bioscience Jan 1;9:1-7, 2004. IF=3.60 Weaving LS, Ellaway CJ, Gécz J , Christodoulou J Rett Syndrome: Clinical Review and Genetic Update Journal of Medical Genetics - in press. Invited chaptersGécz J and Gedeon AK SEDL. In: Creighton, T.E (Ed.) Encyclopedia of Molecular Medicine. Willey, 5 Vol. Pp.2875-2876, 2002. Sutherland GR, Gécz J, and Mulley JC Fragile X Syndrome and Other Causes of X-linked Mental Handicap. In: Emery & Rimoin's Principles and Practice of Medical Genetics (4th edition). Churchill Livingstone, 2002. Gécz J and Fish G FRAXE fragile site associated non-specific mental retardation and the FMR2 gene. In: Genetics of Neurobehavioral Disorders. Ed. G. Fish. Humana Press. 2003, p289-306. Gécz J and Savarirayan R Spondyloepiphyseal Dysplasia Tarda. In: Florian Lang (ed): Encyclopedic Reference of Molecular Mechanisms of Disease, 2004. Contact InformationUnit HeadProfessor Jozef Gécz, PhD LocationNeurogenetics Laboratory Mailing AddressNeurogenetics Laboratory Phone/Fax/EmailPh (08) 8161 6339 Fax (08) 8161 7342 Email jozef.gecz@adelaide.edu.au LinksXLMR Update at Greenwood, SC USA AcknowledgementsWe have a range of national and international collaborators who contribute significantly to our research projects. Among these are: Prof. Gill Turner and Dr. Michael Partington, Newcastle, Australia Prof. John Christodoulou, Sydney, Australia A/Prof. Jamie Craig, Adelaide, Australia Drs. Anne Voss and Tim Thomas, Melbourne, Australia Prof. Hilger Ropers and his group, Berlin, Germany Dr. Laurent Villard, Marseille, France Dr. Lucy Raymond, Cambridge, UK Dr. Charles Schwartz, Greenwood, USA Dr. Dan Geschwind, Los Angels, USA This is a research laboratory, which is currently funded predominantly by Australian NH&MRC. Grants include NH&MRC Program Grant (1x), NH&MRC Project grant (1x) and NH&MRC Fellowship (1x). Other current funding bodies: CAN (Cure Autism Now Foundation), USA RSRF (Rett Syndrome Research Foundation), USA
|
Printer-friendly version