New genetic disorder of balance and cognition discovered

The family of disorders known as ataxia can impair speech, balance and coordination, and have varying levels of severity. Scientists from the Universities of Oxford and Edinburgh have identified a new member of this group of conditions which is connected to 'Lincoln ataxia', so called because it was first found in the relatives of US President Abraham Lincoln. The results are published in the journal PLOS Genetics.

Lincoln ataxia affects the cerebellum, a crucial part of the brain controlling movement and balance. It is caused by an alteration in the gene for 'beta-III spectrin', a protein found in the cerebellum. Each person has two copies of a gene, and in Lincoln ataxia there is an alteration in only one of the two copies. Unexpectedly, the British scientists have found cases of alterations in both copies of the gene, causing a novel disorder called 'SPARCA1' which is associated with a severe childhood ataxia and 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 Lincoln ataxia and SPARCA1.

The work was done using whole , a relatively new technology which allows all of a person's genetics information to be analysed. In addition to sequencing work, the scientists characterized the condition using mice lacking beta-III spectrin. This analysis, combined with previous work, links the protein defect to changes in nerve-cell shape in the associated with cognition and coordinated movements. The work shows that loss of normal beta-III spectrin function underlies both SPARCA 1 and Lincoln ataxia, but a greater loss of beta-III spectrin is required before cognition problems arise.

The combination of methods used in this study highlight a broad role for spectrin in normal beyond the cerebellum. 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".

add to favorites email to friend print save as pdf

Related Stories

Defective protein is a double hit for ataxia

Apr 05, 2010

The neurodegenerative disease spinocerebellar ataxia type 5 (SCA5) damages nerve cells in two ways. University of Minnesota researchers now report that the defective protein responsible for the disease cuts ...

Ghost Protein Leaves Fresh Tracks in the Cell

Oct 30, 2006

Spectrin and ankyrin are two essential proteins acting like bricks and mortar to shape and fortify cell membranes. But distinguishing which protein is the brick and which is the mortar has turned out to be difficult. New ...

New cerebellar ataxia gene identified in dogs

Jun 18, 2012

Researchers at the University of Helsinki and the Folkhälsan Research Center, Finland, have identified the genetic cause of early-onset progressive cerebellar degeneration the Finnish Hound dog breed. The study, led ...

DNA detectives track down nerve disorder cause

Aug 23, 2012

Better diagnosis and treatment of a crippling inherited nerve disorder may be just around the corner thanks to an international team that spanned Asia, Europe and the United States. The team had been hunting DNA strands for ...

Recommended for you

A nucleotide change could initiate fragile X syndrome

19 hours ago

Researchers reveal how the alteration of a single nucleotide—the basic building block of DNA—could initiate fragile X syndrome, the most common inherited form of intellectual disability. The study appears ...

Gene clues to glaucoma risk

Aug 31, 2014

Scientists on Sunday said they had identified six genetic variants linked to glaucoma, a discovery that should help earlier diagnosis and better treatment for this often-debilitating eye disease.

Mutation disables innate immune system

Aug 29, 2014

A Ludwig Maximilian University of Munich team has shown that defects in the JAGN1 gene inhibit the function of a specific type of white blood cells, and account for a rare congenital immune deficiency that ...

Study identifies genetic change in autism-related gene

Aug 28, 2014

A new study from Bradley Hospital has identified a genetic change in a recently identified autism-associated gene, which may provide further insight into the causes of autism. The study, now published online in the Journal of ...

NIH issues finalized policy on genomic data sharing

Aug 27, 2014

The National Institutes of Health has issued a final NIH Genomic Data Sharing (GDS) policy to promote data sharing as a way to speed the translation of data into knowledge, products and procedures that improve health while ...

User comments