Posted 11 July 2022

Unexpected discovery offers rare disease hope
associate Professor Mark Chong

Scientists at SVI have made a ‘surprising’ new finding that may support improved screening, diagnosis and treatment targets for the rare and fatal genetic condition MMIHS (also known as Berdon Syndrome).

An extremely rare disease affecting the bladder, gastrointestinal system and kidneys, MMIHS (Megacystis Microcolon Intestinal Hypoperistalsis Syndrome) impairs the body’s ability to move food along the digestive track and to expel urine. MMIHS is incurable and the average life-expectancy of babies diagnosed is less than six months, with only a handful of affected individuals surviving to early adulthood.

“My lab has for a number of years been investigating a gene called MYL9, due to its association with bone marrow abnormalities. But this gene’s basic function in the body has never been well understood,” explains Associate Professor Mark Chong, Head of SVI’s Genomics & immunology Laboratory.

“Two emerging reports of changes in MYL9 being found in patients with MMIHS prompted us to return to the question of what this gene actually does – and the result of this research quite surprised us all.”

“When we shut off the action of MYL9 in mice, they developed the same bladder and intestinal disease as MMIHS patients – proving that changes in MYL9 are indeed an underlying genetic and molecular cause of this devastating disease.”

Key to the puzzle appears to be MYL9’s role in activating smooth muscle cells, which drive the mechanics of our organs. In the case of the intestine, smooth muscle is responsible for the contractions that propel digested food along in order for nutrients to be absorbed into the body.

“Smooth muscle dysfunction is the most likely cause of the abnormalities observed in the intestine, bladder and lung of MYL9-deficient mice and – similarly – in humans with MMIHS and other related diseases,” says Mark.

He is excited by the potential of his team’s gene discovery: “It provides a new molecular pathway for potential drug targeting. Drugs that can treat MMIHS’ intestinal and bladder effects are critically needed to extend the life-expectancy of those diagnosed and improve their quality of life.”

“MYL9 deficiency is neonatal lethal in mice due to abnormalities in the lung and the muscularis propria of the bladder and intestine” has been published online in PLoS One.


This was research was supported by grants from the National Health and Medical Research Council, Diabetes Australia, US Department of Defense and the Perpetual Foundation The Ann Helene Toakley Charitable Endowment.