research

bruce lefroy centre for genetic health research

summary

The Bruce Lefroy Centre for Genetic Health Research is a research group within the Murdoch Childrens Research Institute, made possible by the generosity of the Lefroy family and friends. The Centre benefits from the synergy between the Murdoch Childrens and VCGS, the major provider of clinical genetics service to Victoria and Tasmania.

The Bruce Lefroy Centre studies genetic diseases of the nervous system including Friedreich ataxia, Parkinson disease, brain malformations, dystonia and Huntington disease. In addition it conducts research into genetic screening. This includes screening for reproductive risk such as for cystic fibrosis, Tay Sachs disease and thalassaemia as well as screening for conditions that can affect the health of the screened individual including haemochromatosis.

The vision of the Bruce Lefroy Centre for Genetic Health Research is to be a centre of excellence in genetic research that contributes to better health in Australia and internationally. Our mission is to create knowledge that will benefit individuals, families and communities affected by genetic conditions.

group leader(s)

Martin Delatycki

  A/Professor Martin Delatycki
  Director, Bruce Lefroy Centre for Genetic Health Research
  Clinical Geneticist
  Genetic Health Services Victoria
  Murdoch Childrens Research Institute
  Royal Children's Hospital
  Flemington Road Parkville, 3052
  Victoria AUSTRALIA

  T  +61 3 8341 6284
  E  martin.delatycki@ghsv.org.au

group leader biography

 

 

 

 

Doctor Paul Lockhart
Bruce Lefroy Centre for Genetic Health Research
Genetic Health Services Victoria
Murdoch Childrens Research Institute
Royal Children's Hospital
Flemington Road Parkville, 3052
Victoria AUSTRALIA

T +61 3 8341 6322
E paul.lockhart@mcri.edu.au

group leader biography

current research projects

Project 1:  Community Genetics

Screening
We are evaluating how carrier testing for genetic conditions that may affect the offspring of individuals is offered to the community.  This includes assessments of screening programs for cystic fibrosis, Tay Sachs disease and thalassaemia. We are also studying the screening for haemochromatosis in high school students in a program called ironXS (http://www.ironxs.com.au)

Ethics

The recent explosion in genetic knowledge has created controversial ethical debates. The following projects aim to gather evidence to inform policy.

Genetic selection for deafness
This study aims to document the views of hearing individuals who have deaf parents about genetic selection for deafness.

Predictive genetic testing in minors
Individuals with a family history of late-onset disorders such as Huntington disease and breast cancer can have testing to predict whether or not they will develop the condition in the future. Guidelines recommend against predictive testing in minors. This project studies the experiences of young people, to provide data to inform evidence-based guidelines.

Project 2:  Friedreich Ataxia

Friedreich ataxia is a severe neurodegenerative condition. Research consists of both a clinical arm and a laboratory arm. The teams work together integrating both laboratory and clinical facets.

Clinical Research

We are investigating therapies for people affected by this condition. This is being done in the setting of a Dedicated Friedreich Ataxia Clinic {http://www.fara.org.au} and involves several collaborations both nationally and internationally.
Projects include:

Assessment of scales and other outcome measures for use in clinical trials
Assessment of vision and eye movements, analysis of speech, assessment of heart function, assessment of hearing, assessment of cognition, upper limb function and functional MRI studies, clinical trials of pharmaceuticals including deferiprone

Laboratory Research

Projects include:

Development of genomic reporter assays to enable high throughput screening of pharmacological agents and to study gene regulation and pharmaceutical evaluation in a whole animal model
Analysis of regulatory mechanisms of FXN gene expression utilising comparative genomics, genomic reporters and small plasmid reporter constructs
Development of accurate 'humanised' mouse models of Friedreich ataxia
Evaluation of the molecular and epigenetic alterations in Friedreich ataxia
Development and characterisation of lentiviral vectors for gene therapy of Friedreich ataxia

Project 3:  Neurogenetics

Complex disorders of the brain constitute one of the largest health, economic and social burdens in the developed world. These disorders affect both the young and elderly and typically are chronic and debilitating. The ultimate goal of our research is to develop therapeutic strategies to prevent or delay disease development and progression.

Parkinson Disease 

Parkinson's disease (PD) is a common age-associated degenerative disease. We are investigating the function of several genes involved in Parkinson's disease by determining when and where the genes are expressed in the brain. 

Dystonia

The dystonias are a group of relatively common neurological movement disorders that generally manifest during childhood and early adulthood. We are interested in determining how a mutation of the torsinA gene results in dystonia utilising cell culture models and patient samples.

Huntington Disease

Huntington disease is a devastating genetic disease of the brain. We are investigating whether lifestyle factors affect the age of onset of symptoms. Our study, involving 154 individuals in Australia and New Zealand, suggests that indeed a delay in onset of several years may be attained by adopting an active lifestyle. We are establishing an international collaboration to replicate this study in a larger population.

Genetics of Brain Development 

Project 4:  Master of Health Sciences (Genetic Counselling)

The Masters (MHSc) is offered to students who have completed the Graduate Diploma in Genetic Counselling. It is a one year supervised research masters, involving original student research with a 30,000 word thesis(http://www.paediatrics.unimelb.edu.au/rhd/master.html).

Over the past few years we have had several students enrolled who have produced diverse and important research using both qualitative and quantitative methodology. This research includes: experiences of parents at the time of diagnosis, developing models of counselling for people who have an intersex condition, the experiences of men with cancer.

team members

  • Louise Corben - Research Coordinator
  • Nicole Cousens - PhD Student (UoM Paeds)
  • Lara Dolling - PROJECT OFFICER
  • Marguerite Evans-Galea - HONORARY FELLOW
  • Liane Ioannou - PhD Student (Monash Medicine)
  • Cara Mand - PhD Student Lapsed (Monash Med)
  • Sarah Stephenson - PhD Student (UoM Paeds)
  • Geneieve Tai - Research Assistant
  • Adam Vogel - Research Assistant
  • Gabrielle Wilson - POSTDOCTORATE RESEARCH FELLOW
  • Michelle Wolthuizen - Project Coordinator
  • Eppie Yiu - PhD Student (UoM Paeds)

publications

  • Botto LD., Feldkamp ML., Amar E., Carey JC., Castilla EE., Clementi M., Cocchi G., de Walle HEK., Halliday J., Leoncini E., Li Z., Lowry RB., Marengo LK., Martinez-Frias ML., Merlob P., Morgan M., Munoz LL., Rissmann A., Ritvanen A., Scarano G., Mastroiacovo P. Acardia: Epidemiologic Findings and Literature Review From the International Clearinghouse for Birth Defects Surveillance and Research. AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS (4) : 262 - 273(2011) PubMed
  • Chartier-Harlin M-C., Dachsel JC., Vilarino-Guell C., Lincoln SJ., Lepretre F., Hulihan MM., Kachergus J., Milnerwood AJ., Tapia L., Song M-S., Le Rhun E., Mutez E., Larvor L., Duflot A., Vanbesien-Mailliot C., Kreisler A., Ross OA., Nishioka K., Soto-Ortolaza AI., Cobb SA., Melrose HL., Behrouz B., Keeling BH., Bacon JA., Hentati E., Williams L., Yanagiya A., Sonenberg N., Lockhart PJ., Zubair AC., Uitti RJ., Aasly JO., Krygowska-Wajs A., Opala G., Wszolek ZK., Frigerio R., Maraganore DM., Gosal D., Lynch T., Hutchinson M., Bentivoglio AR., Valente EM., Nichols WC., Pankratz N., Foroud T., Gibson RA., Hentati F., Dickson DW., Destee A., Farrer MJ. Translation initiator EIF4G1 mutations in familial parkinson disease. American Journal of Human Genetics 89 (3) : 398 - 406(2011) PubMed
  • Corben L., Downie S., Fielding L. Development and trial of an upper limb assessment tool for the acute neurological patient. BRITISH JOURNAL OF OCCUPATIONAL THERAPY 74 (2) : 95 - 105(2011)
  • Corben LA., Akhlaghi H., Georgiou-Karistianis N., Bradshaw JL., Egan GF., Storey E., Churchyard AJ., Delatycki MB. Impaired inhibition of prepotent motor tendencies in Friedreich ataxia demonstrated by the Simon interference task. BRAIN AND COGNITION 76 (1) : 140 - 145(2011) PubMed
  • Corben LA., Delatycki MB., Bradshaw JL., Churchyard AJ., Georgiou-Karistianis N. Utilisation of Advance Motor Information is Impaired in Friedreich Ataxia. CEREBELLUM 10 (4) : 793 - 803(2011) PubMed
  • Corben LA., Georgiou-Karistianis N., Bradshaw JL., Hocking DR., Churchyard AJ., Delatycki MB. The Fitts task reveals impairments in planning and online control of movement in Friedreich ataxia: reduced cerebellar-cortico connectivity?. NEUROSCIENCE (2011) PubMed
  • Delatycki MB. The ethics of screening for disease. PATHOLOGY (2012) PubMed
  • Evans-Galea MV., Corben LA., Hasell J., Galea CA., Fahey MC., du Sart D., Delatycki MB. A novel deletion-insertion mutation identified in exon 3 of FXN in two siblings with a severe Friedreich ataxia phenotype. Neurogenetics 12 (4) : 307 - 313(2011) PubMed
  • Folker JE., Murdoch BE., Cahill LM., Rosen KM., Delatycki MB., Corben LA., Vogel AP. Articulatory kinematics in the dysarthria associated with Friedreich's ataxia. Motor Control 15 (3) : 376 - 389(2011) PubMed
  • Forrest L., Delatycki M., Curnow L., Skene L., Aitken M. An audit of clinical service examining the uptake of genetic testing by at-risk family members. Genetics in medicine : official journal of the American College of Medical Genetics 14 (1) : 122 - 8(2012) PubMed
  • Herlihy AS., Gillam L., Halliday JL., McLachlan RI. Postnatal screening for Klinefelter syndrome: is there a rationale?. ACTA PAEDIATRICA 100 (6) : 923 - 933(2011) PubMed
  • Hickerton CL., Aitken M., Hodgson J., Delatycki MB. "Did you find that out in time?": New life trajectories of parents who choose to continue a pregnancy where a genetic disorder is diagnosed or likely. AMERICAN JOURNAL OF MEDICAL GENETICS PART A (2011) PubMed
  • Holloway TP., Rowley SM., Delatycki MB., Sarsero JP. Detection of interruptions in the GAA trinucleotide repeat expansion in the FXN gene of Friedreich ataxia. BIOTECHNIQUES 50 (3) : 182 (2011) PubMed
  • Kelly M., Bagnall RD., Peverill RE., Donelan L., Corben L., Delatycki MB., Semsarian C. A polymorphic miR-155 binding site in AGTR1 is associated with cardiac hypertrophy in Friedreich ataxia. Journal of Molecular and Cellular Cardiology 51 (5) : 848 - 854(2011) PubMed
  • Klopper F., Delatycki MB., Corben LA., Bradshaw JL., Rance G., Georgiou-Karistianis N. The Test of Everyday Attention Reveals Significant Sustained Volitional Attention and Working Memory Deficits in Friedreich Ataxia. JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY 17 (1) : 196 - 200(2011) PubMed
  • Mill P., Lockhart PJ., Fitzpatrick E., Mountford HS., Hall EA., Reijns MAM., Keighren M., Bahlo M., Bromhead CJ., Budd P., Aftimos S., Delatycki MB., Savarirayan R., Jackson IJ., Amor DJ. Human and Mouse Mutations in WDR35 Cause Short-Rib Polydactyly Syndromes Due to Abnormal Ciliogenesis. American Journal of Human Genetics 88 (4) : 508 - 515(2011) PubMed
  • Mottram PM., Delatycki MB., Donelan L., Gelman JS., Corben L., Peverill RE. Early Changes in Left Ventricular Long-Axis Function in Friedreich Ataxia: Relation with the FXN Gene Mutation and Cardiac Structural Change. JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY 24 (7) : 782 - 789(2011) PubMed
  • Puspasari N., Rowley SM., Gordon L., Lockhart PJ., Ioannou PA., Delatycki MB., Sarsero JP. Long Range Regulation of Human FXN Gene Expression. PLOS ONE 6 (7) (2011) PubMed
  • Rosen KM., Folker JE., Murdoch BE., Vogel AP., Cahill LM., Delatycki MB., Corben LA. Measures of spectral change and their application to habitual, slow, and clear speaking modes. INTERNATIONAL JOURNAL OF SPEECH-LANGUAGE PATHOLOGY 13 (2) : 165 - 173(2011) PubMed
  • Rosen KM., Folker JE., Murdoch BE., Vogel AP., Cahill LM., Delatycki MB., Corben LA. Spectral measures of the effects of Friedreich's ataxia on speech. INTERNATIONAL JOURNAL OF SPEECH-LANGUAGE PATHOLOGY 13 (4) : 329 - 334(2011) PubMed
  • Yiu EM., Geevasinga N., Nicholson GA., Fagan ER., Ryan MM., Ouvrier RA. A retrospective review of X-linked Charcot-Marie-Tooth disease in childhood. NEUROLOGY 76 (5) : 461 - 466(2011) PubMed