Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The family of disorders known as ataxias can impair speech, balance and coordination, and have varying levels of severity. A team led by Dr Andrea Nemeth from NDCN has identified a new member of this group of conditions which is connected to Spinocerebellar Ataxia Type 5 (SCA5). SCA5 is sometimes known as ‘Lincoln ataxia,’ because it was first found in the relatives of US President Abraham Lincoln.

SCA5 is caused by dominant mutations in the gene for ‘beta-III spectrin’, a membrane scaffold protein known to play an important role in the cerebellum. Publishing in PLOS Genetics, the team have identified a more serious recessive ataxia related to SCA5 which is caused by a homozygous stop codon mutation in the beta-III spectrin gene. The homozygous condition causes a novel disorder named ‘SPARCA1’ (Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1), which is associated with a severe childhood ataxia and marked cognitive impairment.

This is the first report of any spectrin-related disorder where both copies of the gene are faulty and has given important insights into both SCA5 and SPARCA1.

Whole genome sequencing and genome-wide mapping, performed at the Wellcome Trust Centre for Human Genetics in Oxford, in addition to the characterization of brain abnormalities in beta-III spectrin knockout mice by team members from Edinburgh (led by Dr Mandy Jackson, who obtained her DPhil at the now Weatherall Institute for Molecular Medicine in Oxford) links the beta-III spectrin defect to changes in nerve-cell shape in brain areas associated with cognition and coordination of movements. The work shows that loss of normal beta-III spectrin function underlies both SPARCA1 and SCA5, but a greater loss of beta-III spectrin is required before cognition problems arise.

This study provides novel evidence for a broad role of spectrin in normal brain function beyond the cerebellum, in both cortical brain development and cognition. There are many brain spectrins and the team are now searching for other abnormalities of spectrin function, as they believe these are part of an expanding group of conditions known as “neuronal spectrinopathies”.

For the full paper please visit the PLOS Genetics website.

Similar stories

European Platform for Neurodegenerative Diseases launches repository of cohorts for researchers

The new Cohort Catalogue will facilitate discovery of over 60 neurodegeneration research cohorts from 17 countries across Europe

Two NDCN students join BNA Scholars Programme

The British Neuroscience Association Scholars Programme was launched in 2021 with a view to improving equality, diversity and inclusion in neuroscience.

Researchers win UK Dementia Research Institute Grand Challenge Award to identify early signs of Alzheimer's

The MRC Brain Network Dynamics Unit has received funding for a multi-year research partnership designed to advance the understanding of early changes to the operations of brain circuits in Alzheimer's disease.

Ophthalmology Conference in Kyiv

On 21 February, Robert MacLaren organised a one-day ophthalmology conference in Kyiv together with Dr Andrii Ruban, President of the Ukrainian Vitreoretinal Society.

Ashmolean turns red for World Encephalitis Day

Our researchers are tackling the devastating brain condition encephalitis.

Bioelectronic implant offers an intelligent therapy to treat incontinence

The first participants in a clinical trial of a bioelectrical therapy to treat incontinence have received their 'smart' bioelectronic implants.