Genetic cause of rare bone disorder discovered

The genetic cause of a rare condition which affects bone and brain development has been discovered in a study led by the UCL Institute of Child Health (ICH). 

The findings, published in the journal Nature Genetics, shed new light on a key enzyme involved in bone development and maintenance, which could be the target of future therapies to treat rare and more common conditions like osteoporosis.

The international study, led by the ICH, identified the mutated gene in people with a condition known as Lenz-Majewski Syndrome (LMS). Ten people worldwide are known to have the condition.

LMS causes progressive problems such as excess bone density and bone malformations, shortness or fusing of fingers and toes, tooth and skin defects as well as affecting the brain. No treatment is currently available for the disorder.

The team found that the condition is linked to an anomaly in phospholipid production, which is an essential component of all human cell membranes. The study identified mutations in an enzyme called phosphatidylserine synthase 1 that produces phosphatidylserine. The mutations lead to a very rare mechanism of disease: they activate the enzyme and cause its regulatory dysfunction which affects the brain, where phosphatidylserine is needed in high amounts, and bone metabolism.

Professor Gudrun Moore, UCL Institute of Child Health, says: “Phosphatidylserine and its fatty acid chains are well-known components of nutritional supplements. Better understanding of the functional role of this enzyme and the consequences of the mutations identified in this study will help to clarify the effect and potential therapeutic use of these different types of supplements.

“A better understanding of the role of phosphatidylserine in normal brain and bone development opens up the potential for developing therapies, not only for this rare disease but also for more common conditions such as osteoporosis.”