Accelerated Gene Identification Program (Gene Discovery)

Project Details

Each year almost eight million children, representing about six per cent of births worldwide, are born with a serious genetic birth defect. For more than half of these conditions, the genetic cause remains unknown. This study, which has been running since 2008, aims to understand the cause of these genetic conditions using new genetic testing technologies such as next generation DNA sequencing. This research allows us to expand our current clinical services to facilitate quicker diagnosis and more extensive genetic counselling for families with rare genetic conditions. This project encompasses a multi-disciplinary team including clinicians, researchers, biostatisticians and genetic counsellors, based at the Murdoch Childrens Research Institute, Victorian Clinical Genetics Services, Royal Children's Hospital, and the Walter & Eliza Hall Institute of Medical Research.  A specific focus is on genetic causes of brain malformations.


We collaborate with a range of different groups including those from the Royal Children's Hospital Melbourne, Murdoch Childrens Research Institute, University of Melbourne.  Our principle local collaborators are A/Prof Paul Lockhart, Professor Martin Delatycki and Dr Rick Leventer (Accelerated Gene Identification Program), A/Prof Melanie Bahlo (bioinformatics lead for the AGIP Program), Prof Jane Halliday (IVF studies and epidemiology), Dr David Godler (epigenetics and Fragile X), Prof Katrina Williams (Autism research), Prof Dinah Reddihough (cerebral palsy research), A/Prof Angela Morgan (Genetics of speech and language disorders).


We are funded through NHMRC and various philanthropic organisations.

Research Outcomes

  • Mill P, Lockhart PJ, Fitzpatrick E, Mountford HS, Hall EA, Reijns MA, Keighren M, Bahlo M, Bromhead CJ, Budd P, Aftimos A, Delatycki MB, Savarirayan R, Jackson IJ, Amor DJ (2011) Human and Mouse Mutations in WDR35 Cause Short-Rib Polydactyly Syndromes Due to Abnormal Ciliogenesis. Am J Hum Genet 88:508-15
  • Smith KR, Bromhead CJ, Hildebrand MS, Shearer AE, Lockhart PJ, Najmabadi H, Leventer RJ, McGillivray G, Amor DJ, Smith RJ and Bahlo M (2011). Reducing the exome search space for Mendelian diseases using genetic linkage analysis of exome genotypes. Genome Biology 12:R85
  • Wilson G, Sunley J, Smith KR, Pope K, Bromhead CJ, Fitzpatrick E, Di Rocco M, van Steensel M, Coman DJ, Leventer RJ, Delatycki MB, Amor DJ, Bahlo M, Lockhart PJ. (2014) Mutations in SH3PXD2B cause Borrone dermato-cardio-skeletal syndrome. Eur J Hum Genet 22:741-7
  • Sim JCH, White SM, Fitzpatrick E, Wilson GR, Gillies G, Pope K, Mountford HS, Torring PM, McKee S, Vulto-van Silfhout AT, Jhangiani SM, Muzny DM, Leventer RJ, Delatycki MB, Amor DJ, Lockhart PJ (2014). Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency. Orphanet  J Rare Disorders 9:43
  • Smith KR, Leventer RJ, Mackay MT, Pope K, Gillies G, Delatycki MB, Amor DJ, Bahlo M, Lockhart PJ (2014). A novel RNF213 mutation causes heterogeneous intracerebral vasculopathy in a family of European ancestry. Int J Stroke 9:E26-7.
  • Lessel D, Vaz B, Halder S,  Lockhart PJ, Marinovic-Terzic I, Lopez-Mosqueda J, Philipp M, Sim JCH, Smith KR, Oehler J, Cabrera E, Freire R, Pope K, Nahid A, Norris F, Leventer RJ, Delatycki MB, Barbi G, von Ameln S, Högel J, Degoricija M, Fertig R, Burkhalter MD, Hofmann K, Thiele H, Altmüller J, Nürnberg G, Nürnberg P, Bahlo M, Martin GM, Aalfs CM, Oshima J, Terzic J, Amor DJ, Dikic I, Ramadan K, Kubisch C (2014) Mutations in SPRTN cause early-onset hepatocellular carcinoma, genomic instability and progeroid features, Nature Genetics 46:1239-44
  • Wilson GR, Sim J, McLean C, Giannandrea M, Galea CA, Riseley J, Fitzpatrick E, Haas SA, Pope K, Hogan KJ, Gregg RG, Stephenson SEM, Bromhead CJ, Wargowski DS, Lawrence CH, James PA, Churchyard A, Phelan D, Gillies G, Salce N, Stanford L, Marsh A, Mignogna M, Hayflick SJ, Leventer RJ, Delatycki MB, Mellick GD, Kalscheuer VM, D’Adamo P, Bahlo M, Amor DJ, Lockhart PJ (2014). Mutations in RAB39B cause X-linked intellectual disability and early onset Parkinson disease with α-synuclein pathology. Am J Hum Genet 95:729-35
  • Leventer RJ, Scerri T, Marsh A, Pope K, Gillies G, Maixner W, MacGregor D, Harvey AS, Delatycki M, Amor D, Crino P, Bahlo M, Lockhart PJ. (2015) Hemispheric cortical dysplasia secondary to a mosaic somatic mutation in MTOR Neurology 84:2029-32
  • Scerri T, Riseley JR, Gillies G, Pope K, Burgess R, Mandelstam SA, Dibbens L, Chow CW, Maixner W, Harvey AS, Jackson GD, Amor DJ, Delatycki MB, Crino PB, Berkovic SF, Scheffer IE, Bahlo M, Lockhart PJ, Leventer RJ (2015) Familial cortical dysplasia type IIA caused by a germline mutation in DEPDC5. Annals of Clinical and Translational Neurology 2:575-80
  • Marsh APL, Lukic V, Pope K, Bromhead CJ, Tankard R, Ryan MM, Yiu EM, Sim JCH, Delatycki M, Amor DJ, McGillivray G, Sherr EH, Bahlo M, Leventer RJ, Lockhart PJ (2015) Complete callosal agenesis, pontocerebellar hypoplasia and axonal neuropathy due to AMPD2 loss. Neurology: Genetics Aug;1:e16
  • Sim J, Scerri T, Fanjul-Fernández M, Riseley JR, Gillies G, Pope K, van Roozendaal H, Mandelstam SA, McGillivray G, MacGregor D, Kannan L, Maixner W, Harvey AS, Amor DJ,  Delatycki MB, Crino PB, Bahlo M, Lockhart PJ, Leventer RJ (2016) Familial cortical dysplasia caused by mutation in the mTOR regulator NPRL3. Annals of Neurology 79:132-7
  • Phelan DG, Anderson DJ, Howden SE, Wong RC, Hickey PF, Pope K, Wilson GR, Pébay A, Davis AM, Petrou S, Elefanty AG, Stanley EG, James PA, Macciocca I, Bahlo M, Cheung MM, Amor DJ, Elliott DA, Lockhart PJ (2016) .ALPK3-deficient cardiomyocytes generated from patient-derived induced pluripotent stem cells and mutant human embryonic stem cells display abnormal calcium handling and establish that ALPK3 deficiency underlies familial cardiomyopathy. Eur Heart J 37:2586-90
  • Amor DJ, Marsh APL, Storey E, Tankard R, Gillies G, Delatycki MB, Pope K, Bromhead C, Leventer RJ, Bahlo B, Lockhart PJ (2016) Heterozygous mutations in HSD17B4 cause Juvenile peroxisomal D-bifunctional protein deficiency. Neurology Genetics 2:e114
    *Vaz B, Popovic M, Newman JA, Fielden J, Aitkenhead H Halder A, Singh AN, Vendrell I, Fischer R, Torrecilla I, Drobnitzky N, Freire R, Amor DJ, Lockhart PJ, Kessler BM, McKenna GW, Gileadi O, Ramadan K. (2016) Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink Repair. Molecular Cell 64:704-719

Research Group

Murdoch Children’s Research Institute Genetics of Neurodisability

Faculty Research Themes

Child Health

School Research Themes

Child Health in Medicine, Neuroscience & Psychiatry

Key Contact

For further information about this research, please contact the research group leader.

Department / Centre


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