Translational Neurogenomics Group
Neurogenetic disorders are challenging to investigate and manage with the majority remaining undiagnosed. The Translational Neurogenomics Group uses advanced genomic technology for gene discovery and genetic diagnosis in neurogenetic disorders. By bringing this technology into the clinics, we aim to provide an accurate and rapid genetic diagnosis and better address the needs of individuals with disabling inherited neurodegenerative disorders.
Neurogenetic disorders can be debilitating and are hereditary. This means that family members of individuals with neurogenetic orders may be at risk of developing the same disease. Neurogenetic disorders include inherited forms of Parkinson’s disease, loss of coordination (ataxias), lower-limb stiffness and weakness (hereditary spastic paraplegias), involuntary movements (dystonia), and muscle disorders (myopathies).
A genetic diagnosis for individuals and their families can guide clinical investigations and management, enable genetic counselling, and inform reproductive options. However, probably less than 50% of families have access to genetic testing. In those who have accessed genetic testing, diagnostic rates are low, at around 30%, and testing is often incomplete. This may be because limited numbers of genes are tested, or certain types of mutations are missed.
The overarching goal of our group is to improve the lives of patients with inherited neurodegenerative disorders, by developing streamlined, comprehensive genetic testing approaches to boost the diagnostic rate and discover new genes.
At our core is a team of neurologist clinician-scientists focused on improving the diagnosis of neurogenetic disorders. Our fundamental connection with clinical practice enables us to accelerate the translation of these research findings into the clinic to influence care.
Our core studies include establishing the first large whole-genome sequencing for dystonia (more than 100 individuals). Using this database, we discovered and described new dystonia genes such as AOPEP (PMID: 34596301) and VPS16 (PMID: 32808683), which are now included in genetic testing panels across the world.
A/Prof Kumar co-led a whole genome sequencing study into mitochondrial disease (PMID: 35641312), which showed that whole-genome sequencing was an accurate test to detect mutations in DNA within the nucleus (nuclear DNA) as well as in mitochondria (energy unit of the cell – mitochondrial DNA). This information was used to support a successful application to make whole-genome sequencing for mitochondrial disease Medicare rebatable, so that individuals across Australia can access this test.
Furthermore, we showed that sequencing long DNA fragments (targeted Oxford Nanopore sequencing) can be used to detect repeat sequences in the DNA which cause neurological disorders such ataxias and myopathies (PMID: 35245110). Together with Dr Ira Deveson, we have been funded through an MRFF grant to develop this further as a clinical test to replace outdated methods such as repeat primed PCR and Southern Blot.
More recently, A/Prof Kumar was awarded a Medical Research Future Fund (MRFF) grant to support his work for the Monogenic Parkinson’s Disease Australia (MonoPDAus) Study. The MonoPDAus study will sequence 1,000 people with early onset or familial Parkinson's Disease throughout Australia, as a collaborative effort with the Global Parkinson’s Program (GP2) and the Australian Parkinson’s Genetic Study (APGS). Its goal is to use the data to facilitate individuals with genetic Parkinson's disease access to clinical drug trials.
- 2023NPJ Parkinson's disease10.1038/s41531-023-00526-9
Elucidating causative gene variants in hereditary Parkinson's disease in the Global Parkinson's Genetics Program (GP2).
Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis.
- 2022Movement disorders : official journal of the Movement Disorder Society10.1002/mds.28982
Nomenclature of Genetic Movement Disorders: Recommendations of the International Parkinson and Movement Disorder Society Task Force - An Update.
- 2022Science advances10.1126/sciadv.abm5386
Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing.
- 2021Movement disorders : official journal of the Movement Disorder Society10.1002/mds.28804
Biallelic AOPEP Loss-of-Function Variants Cause Progressive Dystonia with Prominent Limb Involvement.