Pinpointing the cause of rare epilepsy

Pinpointing the cause of rare epilepsy

Illuminate newsletter index page, December 2019
December 2019

Professor Melanie Bahlo
Professor Melanie Bahlo and her team created a highly
specialised bioinformatics tool to confirm the genetic
mutations that cause FAME.

A decades-long global study involving Institute bioinformaticians has revealed two new gene mutations that cause a rare type of epilepsy called familial adult myoclonic epilepsy (FAME).

Dr Mark Bennett, Dr Haloom Rafehi and Professor Melanie Bahlo contributed to the study by applying their highly specialised bioinformatics tools to independently confirm the gene mutations caused FAME.

They were also able to trace one of the genetic mutations back to its origin; an individual with a spontaneous mutation who lived more than 5000 years ago.

A disease impacting generations

FAME is a hereditary disease with several subtypes that typically begins in a person’s 20s or 30s. It is a dominant genetic disease, meaning that even though it is rare in the general population, children of affected parents have a 50/50 chance of inheriting the disease.

The Institute team helped to discover mutations – in the genes STARD7 and MARCH6 – that cause FAME2 and FAME3, respectively. These mutations are an unusual type called repeat expansions.

Repeat expansions are difficult to detect, and typically associated with neurological diseases, including Huntington’s disease, ataxia, autism and FAME.

Patients receive answers

To identify the repeat expansions, the researchers developed a highly specialised tool called exSTRa (expanded short tandem repeat algorithm) that searches the entire genome for repeat expansions, even with small data sets.

Dr Bennett said typical analysis methods could not detect repeat expansions, so they had traditionally been ignored as a cause of disease.

“We used exSTRa to independently verify the genes that were mutated in these families with FAME.

"Many of these patients have been waiting for years – even generations – to know the cause of their disease. Thanks to this discovery, they finally have an answer,” Dr Bennett said.

Dr Rafehi also developed software that enabled the team to trace the genetic tree of the MARCH6 mutation back to a single spontaneous mutation 253 generations – or 5000 years – ago. This provides valuable information about the likelihood of it arising again and its pattern of spread.

She said the discovery could help to diagnose patients with FAME and other diseases caused by repeat expansions.

“We know that a genetic diagnosis is very important for patients – it provides answers, and allows them to progress with family planning options and potential treatments.

“Finally, there is a high chance of obtaining a life-changing, definitive genetic diagnosis,” Dr Rafehi said.




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