The research, published in the American Journal of Human Genetics, has led to the identification of a rare condition that causes poor motor control and intellectual disability. The absent protein that causes the syndrome could provide the key to new treatments on a wider scale.
The study, by a team from the UCL Institute of Child Health and Great Ormond Street Hospital (GOSH), identified distinctive characteristics in two unrelated families. The affected children had moderate to severe intellectual disability, progressively coarsening facial features and limited hearing and speech.
The children also had relatively large heads despite having small cerebellums – a part of the brain normally packed with neurons which play a key role in controlling motor function. All the children had limited mobility as a result of this cerebellar atrophy; four could only walk with assistance, and two had not progressed beyond crawling.
The research team used genetic mapping and next generation sequencing to discover a mutated gene shared by the two families. Subsequent comparison of their key features to the GOSH Genetics database identified a third family who also had a mutation in the same gene, bringing the number of children affected by the genetic mutation to seven and confirming the shared characteristics were the result of a distinctive syndrome.
The mutation of the affected gene, Sorting Nexin 14 (SNX14), led to the loss of a protein that the researchers deduced is crucial to the development and maintenance of the cerebellum. By identifying the absent protein, researchers hope they can develop potential drug therapies to arrest neurological degeneration for those with the new syndrome and potentially others with more common related conditions.
Philip Stanier, Professor of Craniofacial Developmental Biology and Genetics at the Institute of Child Health who led the research, said: "We now need to find more individuals affected by the mutated gene so that we can get a clearer picture of the scope and severity of the syndrome. This will enable us to build a fuller understanding of what the SNX14 protein does, and in turn help us to better understand normal and abnormal development of the cerebellum, particularly the process of cerebellar degeneration.
“We can now develop model systems to help us in this task and potentially develop therapeutic treatments that might prevent or alleviate neurodegenerative damage, which leads to loss of both motor and intellectual function."