Prevalence And Genetic Mechanisms Of Neurological And Gynaecological Changes In Women Carrying Small FMR1 Expansions
Funder
National Health and Medical Research Council
Funding Amount
$411,895.00
Summary
Fragile X syndrome is one of the commonest genetic forms of mental retardation. The abnormal gene is passed from mothers to their sons or daughters, on their X chromosome. The gene abnormality is unstable, tending to worsen each time it is passed on. But if this gene abnormality is passed from fathers to their daughters, it does not worsen. Therefore, grandfathers of the affected children on their mother's side, as well as the mothers, may carry a mildly abnormal gene (a premutation), insufficie ....Fragile X syndrome is one of the commonest genetic forms of mental retardation. The abnormal gene is passed from mothers to their sons or daughters, on their X chromosome. The gene abnormality is unstable, tending to worsen each time it is passed on. But if this gene abnormality is passed from fathers to their daughters, it does not worsen. Therefore, grandfathers of the affected children on their mother's side, as well as the mothers, may carry a mildly abnormal gene (a premutation), insufficient to cause mental retardation. However, it has recently been discovered that these grandfathers may develop a syndrome (FXTAS) of tremor, incoordination, slowness of movements and mild dementia in their later years. Women were thought to be protected, as they carry TWO X chromosomes, one of which is normal even if the other has a premutation. But very recent reports suggest that they may also develop the FXTAS syndrome, as well as early menopause. This study aims to see how common and severe these abnormalities are in women who carry the premutation, using clinical, MRI and electronic measurements, and to relate the abnormalities to the severity of the gene malfunction and familial predisposition.Read moreRead less
Defining FMR1 And SNRPN Epigenetic Signatures Associated With Neurodevelopmental Disorders
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Fragile X Syndrome and imprinting disorders such as Prader-Willi Syndrome and Angelman Syndrome are characterised by variable penetrance for intellectual disability, motor delay and autism spectrum disorder. This project aims to investigate the prognostic value of using blood-based biomarker tests and sensitive neuroscience informed measures to predict risk and severity of neuropsychological problems in children affected by these disorders.
Investigating The Pathogenic Mechanism Of Mutations In IQSEC2 Causing Non-syndromic Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$449,016.00
Summary
Intellectual disability is frequent in the population, as many as 1 in every 50 people in the world affected. Mutations in IQSEC2, an X-chromosome gene, cause intellectual disability. We will screen 1000 families with this disability for mutations in IQSEC2, building the picture of disease symptoms, contributing to informed genetic counselling. We will investigate functional impacts of these mutations in neuronal cultures, increasing our understanding of the causes of intellectual disability.
Investigating The Pathogenic Mechanisms Of Mutations In The ARX Homeobox Transcription Factor
Funder
National Health and Medical Research Council
Funding Amount
$596,222.00
Summary
Intellectual disability is frequent in the population with as many as 1 in every 50 people in the world directly affected. The cost to Australia of intellectual disability is estimated at $14 billion annually. ARX is one of the most frequent genes mutated in X chromosome linked intellectual disability. Our study will specifically address the functional impact of these mutations using cell models relevant to the brain to better understand the pathways and networks required for normal cognition.