Institute for Neuroscience and Muscle Research

Lab head: Kathryn North
Location: Level 3, Research Building, Kids Research Institute, Children's Hospital at Westmead

Lab members: 1 Laboratory Head, 6 Postdoctoral Fellows, 9 PhD students, 3 Undergraduate Research students, 1 Research Assistant.
Funding: NHMRC, ARC
Research approach equipment: We use DNA sequencing, bio-informatics, mouse models of disease, tissue culture, flow cytometry, immunohistochemistry, Western blotting and biochemical approaches in our research.

Clarke NF, Smith RLL, Bahlo M, North KN. A Novel X-linked form of Congenital Fibre Type Disproportion. Annals of Neurology 2005;58:767-772

Clarke NF, Waddell L, Perry M, Smith RLL, Kornberg A, Muntoni F, Straub V, Bushby K, Guglieri M, King M, Farrell M, Marty I, Lunardi J, Monnier N, North KN. Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion. Human Mutation 2010;31:E1544-E1550

Genetic studies in congenital fibre type disproportion

Primary supervisor: Nigel Clarke

Project description:

Congenital fibre type disproportion (CFTD) is a type of genetic muscle disease that comes under the diagnostic umbrella of the congenital myopathies. The main diagnostic feature on muscle biopsy is consistent smallness of type 1 (slow twitch) muscle fibres compared to type 2 (fast twitch) muscle fibres. Patients present with muscle weakness and low muscle tone, usually at birth or in the first few months of life. Our laboratory leads the world in genetic studies on CFTD, having identified ACTA1, TPM3 and RYR1 as genetic causes. Around 40% of patients remain without a genetic diagnosis and the cause for muscle weakness and the disproportion in fibre size is uncertain in most patients. This project capitalises on the large cohort of CFTD patient biopsies and clinical information we have assembled and uses well-established techniques in our laboratory to address the most significant questions in the field.

The main aims of this project are to:

1. Collate clinical, histological and genetic information on the INMR cohort of CFTD patients to investigate genotype/phenotype correlations and to develop an approach to prioritising genetic investigations

2. Sequence selected CFTD patients for the known genetic causes (TPM3, TPM2, ACTA1, MYH7, RYR1).

3. Perform whole genome sequencing in selected CFTD patients in whom the known genetic causes have been excluded to identify new genetic causes.

Discipline: Pathology
Co-supervisors: Leigh Waddell
Keywords: Genetic diseases, Bioinformatics, gene sequencing