Mutations in NNROS gene cause an early onset, lethal microgilopathy
A study published in Acta Neuropathologica identifies mutations in NRROS as a novel microgliopathy. Feb 2020.
Microglia are tissue-resident macrophages playing essential roles in central nervous system development and homeostasis. The importance of microglia for brain health in humans has been highlighted by the definition of Mendelian disorders associated with a disturbance of microglia-related protein function, the so-called microgliopathies. Now, an international consortium led by Yanick Crow, Colin Smith, Jack Barrington and Barry McColl, from the Institute of Genetics and Molecular Medicine (YC), the Centre for Clinical Brain Sciences (CS), and the Centre for Discovery Brain Sciences and the UK Dementia Research Institute (JB, BMcC) in Edinburgh, describe a novel microgliopathy due to mutations in NRROS.
In work partly funded by the RS MacDonald Charitable Trust, three patients were identified demonstrating a highly stereotyped clinical and radiological phenotype comprising initially normal development, followed by the onset of epilepsy and a loss of skills in the second year of life, and then death by age 3 years. Study of the brain of one child revealed features consistent with a mouse model of NRROS deficiency, and transcriptomic analyses showed that brain expression of NRROS is highly localised to microglia in humans and mice. These findings indicate that NRROS is indispensable in controlling the early development of a homeostatic microglial population, and/or its ongoing preservation in the postnatal brain, and define a loss of NRROS function as a novel microgliopathy in humans. Further studies to explore the cellular pathology underlying with this fatal encephalopathy are warranted.
Publication in Acta Neuropathologica https://doi.org/10.1007/s00401-020-02137-7
Prof Yanick Crow Research group webpage